A food supplement having Adiponectin Agonist properties

doi:10.21203/rs.3.rs-1508261/v1

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Research Article

A food supplement having Adiponectin Agonist properties

https://doi.org/10.21203/rs.3.rs-1508261/v1

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posted 31 Mar, 2022

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Objective

Present work was planned to study the clinical effects of Adipomimetin tablets on human beings having Type-II diabetes.

Research Methods &Procedures:

Tablets were prepared with 40mg and 80mg of Adipomimetin per tablet. They were administered to diabetic patients as an ‘add-on’ to standard-of-care therapy that was stabilized for each patient enrolled; and also to a small group of patients which were diagnosed for the first time as diabetic and had not been started on any medicine.

Results

The findings on ability of Adipomimetin for normalizing blood sugar and hypertension over and above the effect of Standard-of-Care therapy were confirmed in a CTRI registered prospective clinical trial.Statistically highly significant reduction at P < 0.0001 in HbA1c, Fasting and Post Prandinal blood sugar, Systolic blood pressure, body weight, BMI, Diastolic blood pressure at P = 0.0319 and increase in Muscle % at P = 0.0318 was noted. Although overall reduction in body fat was insignificant statistically (P > 0.05), in individuals that had high body fat, reduction in the same was observed.The observations point out tohormonal action ofAdipomimetinas an agonist of Adiponectinthat substantially restores the homeostasis of metabolism to normal level so that its anti-pathogenesis action, i.e. action against genesis of disease, is anti-Metabolic-Syndrome-genesis,rather than a medicinal action that modifies body/metabolism to control the symptoms of diseases after the disease is precipitated. Adipomimetin, a nutraceutical/food supplement, has shown its capability to cover the scope of recovery that has not been covered by State-of-Artmedicinal treatment for above clinical parameters. There was no difference in efficacy between 40mg and 80mg active.

Conclusion

The “water insoluble concentrated mass substantially free from components more soluble in the plant juice” – the Adipomimetin, displays Adiponectin Agonist properties useful to overcome deficiency of Adiponectin and to augment all benefits expected from an Adiponectin Agonist at 40mg active three times a day.

Food Science & Technology

Nutrition & Dietetics

Hypo-adiponetinaemia

Adipomimetin tablets

Type-II diabetes

Standard-of-Care therapy

Fasting sugar

Post Prandinal blood sugar

Metabolic syndrome

Medicine is a chemical entity which is considered as toxic if administered to a normal individual but mitigates a symptom in diseased individual, but also has,in addition, unintended effects some of which may be adverse to varying degrees for the body – the side effects. However, medicines are considered desirable for administration to a diseased individual within a certain range of dosages when its side effects are less adverse than the consequences of symptom of the disease. A significant proportion of adults and geriatric population, multiplicity of medicines with their inevitable side effects and loss of quality life including chronic fatigue is a major issue.

Food/dietary supplement is a productderived from a normally eaten food sourceand contains an active ingredient in concentrated form or in purer isolate form, known for its nutritional or functional benefit to maintain health/metabolic balance/homeostasis. They are normal ingredients usually consumed for several years, typically even millions of years, through its source which is a food raw material and has established safety. Even in concentrated form, they are regarded as non-toxic if they are consumed within the limit in which they are usually contained in the usually consumed quantity or recommended-to-consume quantity of its source raw material,innormal food consumptionpattern.A food/dietary supplementwith health claim goes to the root of a disease/disorder, fulfills a metabolic need/deficiency to restore the balance of metabolism so that symptoms do not arise and medicines are not needed to mitigate the symptoms.

Literature showed that, Adipocyte hormone- Adiponectin plays key role inthe regulation of insulin sensitivity, endothelial function, anti-inflammatory effect and gluconeogenesis so that lifestyle diseases/disorders and finally the Metabolic Syndrome does not arise^1–3. In principle, making up the Adiponectin deficiency could be a most effective strategy to keep most of the medicines away.

It is reported⁵ that an alternative Adiponectin-targeted drug development strategy is to design chemical agonists that can mimic Adiponectin to activate its receptors and/or post-receptor signaling pathways. Such an approach may also be able to reverse ‘Adiponectinresistance’, which has been observed in both animals and humans^{15, 16}.However, since the discovery of the two Adiponectin receptors (AdipoR1 and AdipoR2) in 2003, little progress has been made in the understanding of the structural basis underlying their ligand-receptor interactions⁵.

Possibility of chemical agonists seems remote, particularly because the active site of Adiponectin that attaches itself to the receptors of Adiponectin is a three dimensional structural part of Adiponectin protein, which cannot be made by chemical synthesis. However,Osmotin or Osmotin like proteinsdo share structural similarity wherein the structure of beta barrel of these proteins that has homology with the active site of Adiponectin which attaches to the receptors. These Osmotins or Osmotin-like proteins, also known as PR-5 proteins, are shown to be Adiponectin Agonists,which are ubiquitous in plant world and are produced in plants in response to pathogenic or environmental stress^4,6,11,12. The Osmotins or Osmotin-like proteins have been isolated as 95–99% pure isolate having a single band when subjected to electrophoresis⁶; which is acknowledged as useful for treating a mammal suffering from disorder selected from the group consisting of type II diabetes, insulin resistance, hyperlipidemia, arteriosclerosis, and heart disease. However, the methods of making “isolated PR-5 proteins” are capable of yielding only microgram quantity of the95-99% pure Osmotin composition from kilogram quantities of the raw material. However, since at least few milligram quantities of Osmotin are required per dose for practical use for human being; their Adiponectin Agonist activity could be illustrated only on microorganisms susceptible to them in a test tube^4,7,10 or on experiments on rats ¹⁴; and accessibility to human subjects needing them remained an unfulfilled requirement.

First report on their application in animalsis on rats; wherein both, Osmotin-I and Osmotin-II, when injected to rats resulted in decrease in body weight, serum triglyceride, total serum cholesterol and decreased atherosclerotic lesion area¹⁴. This report has provided first clinical evidence on animals of Osmotins as Adiponectin Agonists. However, with lack of methods to make Osmotinsona large scale, even after a decade of publication of Osmotins or Osmotin-like proteins being shown to be Adiponectin Agonistand claiming a method of treatment using its isolate, access to an agonist of Adiponetcin continued to persist and utility of this knowledge on Osmotins remained only limited to be as a tool in drug delivery researmch⁷.

It has been suggested that the beneficial effects of a diet containing 400 g. of fruits and vegetable may partly be due to the Osmotin content apart from the anti-oxidants and high fiber low fat content⁸.However, this does not fulfill a requirement of a dosage form of Adiponectin Agonist with known dosage and known efficacy for human use to overcome Adiponectin deficiency.

A techno-economically feasible method of making an Adiponectin Agonist composition which is different from earlier disclosed Adiponectin Agonist compositions in that it was not an electrophoretically pure isolate, but was syrup of Juice Soluble free from heat coagulablecomponents of leafy shoot juice⁹.This is a multicomponent mixture containing heat stable proteinsand other juice soluble phytochemicals; and was illustrated to be effective in replacing dose of three 250mg tablets of Metformin three times per day in a 63 year old Type-2 diabetic person for lowering post-prandinal blood sugar level.This syrup was also seen to lower triglycerides and LDL cholesterol on another diabetic person in a span of three months. However,this composition was a sticky, difficult to dry syrup having unpalatable bitter and astringent taste, was required to consume three spoonful (4.5 ml per spoon) as each dose with each meal; was difficult for dispensing for accurate dosing and for carrying to workplace or using the same while travelling. Thus, this work did provide a start for an Adiponectin Agonist composition capable of being manufactured at a scale required for making its use for human subjects practically possible for the first time, yet improvement was needed in the product itself. Further, it was seen that the composition was a highly complex mixture of all juice soluble interacting phytochemicals, including high molecular weight polyphenols, and, as such, was not storage stable, which was indicated by the fact that the efficacy decreased progressively in storage and a two year old composition of same product was totally ineffective.

The much needed improvement has been providedwhen composition comprising heat stable plant juice soluble plant protein was obtained as essentially a water insoluble concentrated mass, essentially free from components more soluble in the plant juice, and enriched in heat stable proteins of the plant juice¹³.In cases studies,the intermediates of this process and the final concentrated mass, all administered at a level of 80mg dry weight per dose with food, three times a day, showed evidence of Adiponectin Agonist propertiesin case studies. The said evidence included drop in blood sugar level below renal threshold in just one dose when consumed as“add-on” to the stabilized treatment of Metformin and successful stepwise replacement of Metformin treatment ina span of 3 weeks. After the replacement, the blood sugar levels never reached the levels for up to three years over the level which prevailed when only Metformin treatment was being taken continuously as a stabilized treatment. Concurrent to replacement of Metformin, chronic fatigue also disappearedresulting in improvement of quality of life. This was also followed, in course of time, in reduction on fasting and post-prandinal blood sugar,normalizing blood pressure and HDL cholesterol.Eleven months after total replacement of Metformin, drop was seen in HbA1calso from 8.6 to 8.16. Metformin replacement was also achieved in a woman aged 58 years with the 80mg (by dry matter) sediment containing syrup; who is continuing with the replacement thereafter with the 80mg dose for more than two years without increase in blood sugar level above at which it existed with Metformin treatment. In a third case of a man of about 50 years, who was diagnosed for the first time with Glucose intolerance and was not started on any medication, blood sugar levels could be brought down with administration of syrup of this concentrate¹³.

One batch of heat stable plant juice soluble plant protein obtained as essentially a water insoluble concentrated mass free from components more soluble in the plant juice, and enriched in heat stable proteins of the plant juicewas named as 7F¹³, from which tablets were made containing 40mg and 80mg of the concentrate per tablet; these tablets showed same efficacy on above three cases, and their replacement of Metformin thereafter is continuing on 40mg tablets for the first subject and on 80mg tablets for second and the third subject.

It was a prospective single centric, parallel group,double arm,assessor-blindedtrial of Adipomimentin as an add-on therapy for the patients having T2DM.Subjects were assigned toeither of the twogroupsrandomly by using computer generated random number list. Group A received 500mg tablet having 40mg of active ingredient, while group B received 500mg tablets having 80mg of active ingredient.The allocation was in the ratio 1:1.Primary outcome sought was to study the efficacy of Tab. Adipomimetin in reducing blood sugar levels in patients with T2DM when given in two different doses and find out the best dose of the two.

Secondary outcome was to see efficacy of Tab. Adipomimetinin enhancing the Quality of Life of patients with T2DM. It was also sought to see overall safety of Tab. Adipomimetinin patients with T2DM

Tablets containing 40mg and 80mg made from heat stable plant juice soluble plant protein obtained as essentially a water insoluble concentrated mass free from components more soluble in the plant juice, and enriched in heat stable proteins of the plant juice¹³ (Adipomimetin) of batch 7F were used in this clinical trial.

Patients were enrolled and data was collected at the out-patient departmentof the study site i.e. Sterling Multispecialty Hospital, Sector 27, NigdiPradhikaran, Pune-411044. Blood Investigations were performed in the laboratory attached to the hospital.

Patients were screened using inclusion and exclusion criteria. Eligible and willing patients were enrolled in the study after due written consenting. After enrollment, patients were assigned to one of the groups by using computer generated random number list. After completing the baseline procedures, appropriate study drug (having either 40 mg or 80 mg active ingredient in it) was dispensed to the patients.Each bottle of tablets contained dose sufficient for 30 days. During follow-ups, further dispensing was done.

Participants providing consent and were under stabilized Standard-of-Care treatment for past at least 3 months were enrolled randomly to 40mg tablets and 80mg tablets groups; wherein the Adipomimetin tablets were given as add-on to their Standard-of-Care treatment. Patients who were diagnosed for the first time as diabetic or pre-diabetic and had not received any standard-of-care treatment were recruited and were assigned randomly to one of the above two groups (40mg tablets group and 80 mg tablets group);as these were pre / newly diagnosed cases, “Standard-of-Care” treatment was not applicable/given to this cohort..

Sponsor had provided 2 boxes at the study site containing 2 different doses of actives. Investigator was aware, who dispensed appropriate drug bottle to the corresponding group-assigned subjectat the day of recruitment and on every 30^thday. Laboratory personnel were unaware (blinded) of the randomization.

Recruitment started on 9^th August 2017 and was concluded on 9^th January 2018.Follow-up was done every 15 days.

HbA1cand lipid profile was determined on the day of enrollment and 90^thday. Fasting and Post-prandinal blood sugar were determined on day of enrolment, 15^th day, 30^thday, 50^th day and 90^thday. Fat analysis and Anthropometric measurements (fat%, Weight, BMR, Metabolic age, Visceral fat, Muscle% were recorded on day of enrolment and on 90^th day. Height, weight, BMI, blood pressure and pulse were recorded on the day of enrollment and 90^thday. Medical history on smoking, alcohol consumption, burn in feet, Heart attack/stroke, hypertension andfamily history of the subject were also recorded.

A total of 36 patients were recruited in the trial and assigned randomly to administration of 40mg or 80mg tablets of Adipomimetin. To ensure applicability of clinical trial results to the entire population, subject to the exclusion criteria, the patients were selected randomly in an unbiased way, such as irrespective of sex, educational qualification, caste, creed and irrespective of whether the patients were urban or rural etc. Hence, the sample was fully representative of the diabetic society at large and the conclusions would be applicable very broadly to every diabetic population. After the trial was over, data of the patients was grouped in two groups based on Standard-of-Care treatment received by them and third group of patients included those who were diagnosed as diabetic or pre-diabetic for first instance and had not received any anti-diabetic Standard-of-Care medicines prior to the enrollment and also not after enrollment until conclusion of the trialand have received the Investigational Product only. The medicines receiving groups were receiving same medicine treatment which they were receiving for at least three months prior to start of the clinical trial which was a standardized and stabilized Standard-of-Care anti-diabetic treatment. Hence, it could be concluded whether the Investigational Product had additional efficacy and also whether it had stand-alone efficacy too.

From the patients enrolled, patients treated with “Metformin + (in some patients) Voglibose and/or Teneligliptin” were considered as group 1. Group 2 patients were treated with “Glymepiride (in most cases or another Sulphonyl Urea in some cases) + Metformin + in some cases Voglibose without or with Teneligliptin”. Group 3 patients include one pre-diabetic and two diabetic patients diagnosed for the first time and were not taking any medicine would serve as normal control (No Standard-of-care treatment) for between-the-groups comparison.

Since the patients of Group 1 and Group 2 are the patients who had a stabilized State-of-Art treatment three months prior to their inclusion in the trial, and they represent all combinations of antidiabetic drugs that are prescribed as Type-II diabetes goes on increasingly/further and further degenerating, these groups represent the maximum achievable control on Type-II diabetes achievable for those patients by State-of-Art treatment; their clinical parameters on day 0 represent “self-control” forwithin-the-group comparison: i.e. to compare whether Adipomimetin gives any additional effect, and if so, whether it is statistically significant over the stabilized state of art treatment represented by day 0 clinical parameters. .

From the patients enrolled, following patients were either omitted from final data taken for statistical analysis or data correction is applied for reasons explained:Patient no. DM3, DM 13, DM 26, DM 27, DM28 were dropped due to exceptionally irregular, unexplainedand un-uniform results.DM5 was dropped because consent was withdrawn. DM9 was dropped because the patient suffered high stress on account of death of husband leading to irregularity in daily routine. DM10 and DM23 weredropped since they were lost to follow-up. DM11 was dropped due to high stress arising from family problems and consequent irregularity in daily routine. DM18 and 19 were dropped because their standard-of-care dose was modified midway by reducing its dose.DM25 and 29 weredropped due to poor compliance i.e. the patients did not consume more than 30 tablets given to him. Blanks in DM-21 in Vitals data of 60 days were extrapolated from the data on preceding and immediately after that period. In DM-22 data on weights was verified from the original case papers again in view some discrepancy; and verified corrected data was entered on body weight.

Statistical analysis

Summary of the statistical analysison all 22 participants retained for analysis is provided in Table 1which is done by ANOVA (Analysis of Variance} of “paired samples”.

The data was analysed for significance of difference between means of an initial observation and observations taken after one or more intervals on the same enrolled participant(paired data).Analysis of Variance (ANOVA) was used, for which t Test and F Test are considered as robust methods of analysis. They do provide “T value” and “F value” that should be exceeded at various levels of significance starting from degrees of freedom of 1 for “T test” and of 1 in numerator and 1 in denominatorfor :F value”, This clinical trial has 22 human subjects on whom observations on clinical parameters are taken for two or five periods provides far bigger sample size that is required minimum for applying “t test” and “F test”; hence, the conclusions drawn on this sample size are robust and valid,During analysis of paired data for F ratio and t test, the calculated p value confirms statistical validity and robustness of the sample size itself.

Since CD (Critical Difference) is useful for determining significance of difference of means of observations on different days, it is regarded that, the CD would also be useful to determine significance of difference between two observations of clinical parameter on two different days of each/individual participant that are part of the same data, and also to determine significance of difference between means of two different days of two different groups of participants of the same group, wherein, the groups are made on the basis of their State-of-Art treatment for Type-II diabetes. Based on above understanding, data was analysed by making various groups of parameters and on the basis of CD based on F ratios for P=0.05 and P=0.01 and also by calculating actual P values. Accordingly, following are the interpretations on the observations on the entire set of data as well as sub-grouping / sub-combinations of the same data.

Thus, Table 1 provides a summary information that Adipomimetin statistically significantly decreasedmean between Day 0 to Day 90 at P=<0.0001 in HbA1c (8.7-7.6), fasting blood sugar (167mg/dl – 124mg/dl), post-prandinal blood sugar (270mg/dl – 191mg/dl), systolic blood pressure (136mm – 121mm), body weight (69.8kg – 67.9kg), BMI (28.4 – 27.6), pulse(80/min – 77/min); and increased muscle% (Muscle% (23.6kg – 24.6kg) at P=0.0318).Diastolic blood pressure decreased during same period (83mm – 78mm) at P=0.0319.

Table 1: Effect of Adipomimetinon physiological and biochemical parameters of the patients

Clinical Parameter (CP)	Means					Actual P value of F ratio	Critical Difference		Degrees of Freedom (DF)
Clinical Parameter (CP)	Day 0	Day 15	Day 30	Day 60	Day 90	Actual P value of F ratio	P=0.05	P=0.01	CP of DF	Total DF
HbA1c	8.7	NA	NA	NA	7.6**	<0.0001	0.43	0.58	4	109
Fasting Blood sugar (mg/dl)	167	137*	132**	128**	124**	<0.0001	22.8	30.3	4	109
Post Prandinal blood sugar mg/dl	270	233*	214**	193**	191**	< 0.0001	30.1	39.9	4	109
Systolic blood pressure (mm of Hg)	136	130*	126**	125**	121**	< 0.0001	5.1	6.8	4	109
Diastolic blood pressure (mm of Hg)	83	79	76**	80	78*	0.0319	4.2	5.6	4	109
Body Weight	69.8	69.6	68.6**	67.9**	67.9**	< 0.0001	0.56	0.75	4	109
BMI	28.6	28.6	28.5	28.2*	27.9**	< 0.0001	0.3	0.4	4	109
Pulse	80	78	77*	77*	77*	0.0664	2.5	3.3	4	109
LDL	106	NA	NA	NA	102	0.581	15.5	21.1	1	43
HDL	50.4	NA	NA	NA	53.6	0.4961	9.5	13	1	43
Cholesterol	166	NA	NA	NA	168.1	0.7823	15.6	21.2	1	43
Triglycerides	105	NA	NA	NA	105.7	0.9249	12.3	16.7	1	43
BMR	1488	NA	NA	NA	1482	0.906	97.2	132	1	43
Visceral fat	13.4	NA	NA	NA	12.4	0.1339	1.3	1.8	1	43
Muscle%	23.6	NA	NA	NA	24.6	0.032	0.9	1.2	1	43

* Difference with reference to Day 0 significant at P= ≤ 0.05, ** Difference with reference to Day 0 significant at P= ≤ 0.001, *, NA - Not Applicable

In all other clinical parameters the differences were statistically non-significant between level at Day 0 and Day 90: such clinical parameter observations were, Low density lipoprotein (LDL) 106mg/dl – 102mg/dl, High Density Lipoprotein (HDL) 50.4mg/dl – 53.6 mg/dl, Cholesterol 166mg/dl – 168.1mg/dl, Triglycerides105.2mg/dl – 105.7mg/dl, BMR (1488 – 1482), Visceral fat (13.4kg – 12.4kg). It may be noted here that on the 0 day itself above averages are within normal range of the respective clinical parameter; and as per expectation of its action as mimetic/agonist of Adiponectin, which is expected to maintain/restore normal balance / homeostasis, Adipomimetin did not modify the clinical parameters which were within normal range; but has brought the same in the direction of normal range only if the parameter at 0 day was in clinically abnormal range. This is indicative of discretionary hormonal action of Adiponectin of maintaining homeostasis to apply correction to imbalance of metabolism, so that symptoms of disease do not arise rather than applying artificial tweaking of metabolism to overcome the disease.This mechanism of action is in contrast to the “Medicinal/indiscrete symptomatic action” of drugs like Sulpholyureas and Insulin wherein they have no discretion of stopping to act when normal clinical levels are approached and they do push the blood sugar level below the normal level also if their dosage is in excess. In other words, Metformin, Sulphonylureas and Insulin and similar anti-diabetic medicines cannot be given to a person who is not diabetic; but Adipomimetin can be given without any concern of harm even to a non-diabetic person; making them highly useful not only to those who are clinically having Type-II diabetes, but also to or those who have not become diabetic but are at risk to become diabetic or are at pre-diabetic level.

Details of clinical parameter-wise and group-wise results are provided in following Tables 2-10.

Table 2: Effect of Adipomimetinon HbA1c levels

Treatment groups	Means HbA1c
Treatment groups	Day 0	Day 90
Group 1:Metformin + (in some patients) Voglibose and/or Teneligliptin + Adipomimetin (80mg or 40 mg three times a day)	8.6	7*
Group 2: Sulphonyl Urea (Glymepiride or any other) + Metformin + occasionally Voglibose without or with Teneligliptin + Adipomimetin (80mg or 40 mg three times a day)	8.9	7.9**
Group 3: Only Adipomimetin tablets (80mg or 40 mg three times a day), no “Standard-of-care” treatment of Medicines	7.9	7.1**
Pooled data of 80mg+40 mg Adipomimetin	8.7	7.6**
Pooled data 80mg Adipomimetin group	8.6	7.9**
Pooled data 40mg Means Adipomimetin group	8.7	7.3**
Pooled data Males group	8.8	7.6**
Pooled data Females group	8.6	7.6**
Critical Difference P=0.05: 0.43
Critical Difference P=0.01: 0.58

Table 3: Effect of Adipomimetinon fasting blood sugar levels

Standard of Care treatment: Stabilized since 3 months pri0r to recruitment	Fasting Blood Sugar (mg/dl) means
	Day 0	Day 15	Day 30	Day 60	Day 90
Group 1:Metformin + (in some patients) Voglibose and/or Teneligliptin + Adipomimetin (80mg or 40mg three times a day)	170.7	138**	126.5**	120.5**	113.2**
Group 2: Sulphonyl Urea (Glymepiride or any other) + Metformin + occasionally Voglibose without or with Teneligliptin + Adipomimetin (80mg or 40mg three times a day)	166.9	139.6*	136.5*	136.4*	129.5**
Group 3: Only Adipomimetin tablets (80mg or 40mg three times a day), no “Standard-of-Care” treatment of Medicines	159.3	125.3**	120**	108.3**	123.7**
Pooled means
Pooled data 80mg+40 mg	166.9	137.2	131.5*	128.2*	124.2**
Pooled data 80mg	160.2	135.6	131.6*	126*	123.6**
Pooled data 40mg Mean	171.5	138.4	131.5*	129.8*	124.7**
Pooled data Male Mean	188.1	132*	123.3**	118.9**	125.3**
Pooled data Female Mean	157	139.7	135.3*	132.6*	123.7**
Critical Difference
P=0.05	22.8
P=0.01	30.2

Table 4: Effect of Adipomimetinon post prandinal blood sugar levels

Standard of Care treatment: Stabilized since 3 months prior to recruitment	Post Prandinal Blood Sugar (mg/dl)
	Day 0	Day 15	Day 30	Day 60	Day 90
Group 1:Metformin + (in some patients) Voglibose and/or Teneligliptin + Adipomimetin (80mg or 40mg three times a day)	238.5	206.7*	199.3*	176.5**	172.5**
Group 2: Sulphonyl Urea (Glymepiride or any other) + Metformin + occasionally Voglibose without or with Teneligliptin + + Adipomimetin (80mg or 40mg three times a day)	280.5	223.1**	213.8**	196.3**	189.8**
Group 3: Only Adipomimetin tablets, no “Standard-of-Care” treatment of Medicines + Adipomimetin (80mg or 40mg three times a day)	289.7	253.3*	241.3**	209.3**	235.3**
Pooled means
Pooled data 80mg+40 mg	270.3	222.7**	213.6**	192.7**	191.3**
Pooled data 80mg	246.1	204.0**	196.1**	178.4**	178.8**
Pooled data 40mg	287	235.7**	225.8**	202.5**	199.9**
Pooled data Male	289.7	235.7**	205.0**	183.0**	192.1**
Pooled data Female	261.2	216.7**	217.7**	197.2**	190.9**
Critical Difference
P=0.05	30.1
P=0.01	39.9

Table 5: Effect of Adipomimetinon systolic blood pressure

Standard of Care treatment: Stabilized since 3 months prior to recruitment	Systolic Blood Pressure(mm of Hg)
	Day 0	Day 15	Day 30	Day 60	Day 90
Group 1:Metformin + (in some patients) Voglibose and/or Teneligliptin + Adipomimetin (80mg or 40mg three times a day)	130	128.3	123.5*	120.0**	123.3*
Group 2: Sulphonyl Urea (Glymepiride or any other) + Metformin + occasionally Voglibose without or with Teneligliptin + + Adipomimetin (80mg or 40mg three times a day)	136.2	129.6*	126.9**	127.3**	120.3**
Group 3: Only Adipomimetin tablets, no “Standard-of-Care” treatment of Medicines + Adipomimetin (80mg or 40mg three times a day)	150	136.9**	123.3**	123.3**	116.7**
Pooled means
Pooled data 80mg+40 mg	136.4	130.2*	125.5**	124.8**	120.6**
Pooled data 80mg	133.2	126.7*	125.6**	125.0**	122.2**
Pooled data 40mg	138.5	132.7*	125.5**	124.6**	119.5**
Pooled data Male	135.7	130.0*	127.1**	129.3**	120.0**
Pooled data Female	136.7	130.3*	124.7**	122.7**	120.9**
Critical Difference
P=0.05	5.1
P=0.01	6.8

Table 6: Effect of Adipomimetinon diastolic blood pressure

Standard of Care treatment: Stabilized since 3 months prior to recruitment	Diastolic Blood Pressure (mm of Hg)
	Day 0	Day 15	Day 30	Day 60	Day 90
Group 1:Metformin + (in some patients) Voglibose and/or Teneligliptin + Adipomimetin (80mg or 40mg three times a day)	80	78.3	73.3**	75.0*	80
Group 2: Sulphonyl Urea (Glymepiride or any other) + Metformin + occasionally Voglibose without or with Teneligliptin + + Adipomimetin (80mg or 40mg three times a day)	82.8	79.5	77.7*	83.5	76.2**
Group 3: Only Adipomimetin tablets, no “Standard-of-Care” treatment of Medicines + Adipomimetin (80mg or 40mg three times a day)	90	76.7**	76.7**	73.3**	80**
Pooled means
Pooled data 80mg+40 mg	83	78.8	76.4**	79.8	77.7*
Pooled data 80mg	78.4	81.1	76.7	79.4	78.9
Pooled data 40mg	86.2	77.2**	76.2**	80.0**	76.9**
Pooled data Male	85.7	77.1**	77.1**	79.3**	78.6**
Pooled data Female	81.7	79.5	76.0*	80	77.3**
Critical Difference
P=0.05	4.2
P=0.01	5.6

Table 7a: Effect of Adipomimetin on Type-II diabetes as well as hypertension: Participants having Type-II diabetes as well as hypertensionand their State-of-Arttreatments and particulars of Adipomimetin tablets administered to them

S. No.	Sex	Standard of Care treatment		Adipomimetin per tablet
		Type-II diabetes	Hypertension and heart disease	Three tablets per day
Group 1:Metformin + (in some patients) Voglibose and/or Teneligliptin
1	F	Glycomet500 1-0-0-1; Metformin 500mg	Telmisartan 1 - 0 – 1	40 mg
Group 2. Glymepiride (in most cases or another Sulphonyl Urea in some cases) + Metformin + in some cases Voglibose without or with Teneligliptin
2	M	Glycomet GP 1-0-0-1: Glimepiride 1 mg and Metformin 500mg	Ramipril 5mg 1 - 0 – 0	80 mg
3	F	Glycomet GP 1-0-0-1: Glimepiride 1 mg and Metformin 500mg	Ramipril 5mg 1 - 0 – 0	40 mg
4	F	Glycomet 500mg 1-0-1: Metformin 500mg	NO medication for BP	40 mg
5	F	Glycomet GP 2 1-0-0-1: Glimepiride 1 mg and Metformin 500mg	Telmisartan H 1 - 0 – 1	80 mg
6	M	Gemer-2 0.5-0-0: Glimepiride 2mg; Glycomet 1-0-1: Metformin 1000mg	Olmesartanmedoxomil 40mg+ Amlodipine 5mg + Hydrochlorothiazide 12,5mg 1-0-0; (Atorvastatin 10mg + Acetylsalicylic acid 75mg	40 mg
7	F	Tab. Glimy M 1-0-0: Glimepiride 1, Metformin 500mg mg; tab. Glycomet 0-0-0-1: Metformin	Ramipril 5mg 1 - 0 – 0	80mg
8	F	Glimy 2 1-0-0: Glimepiride 2 mg+ Metformin 500mg; metadoze -IPR 800 1-0-0:	Ramipril 5mg 1 - 0 – 0	40 mg
8	F	Metformin 500 MG+Voglibose 0.2 MG; Tendia-20 1-0-0: Teneligliptin 20mg	Ramipril 5mg 1 - 0 – 0	40 mg
Group 3: Only Adipomimetin tablets, no “Standard-of-care” treatment of Medicine
9	M	No medicines for Type-II diabetes	NO medicines for BP	40 mg
10	M	No medicines for Type-II diabetes	NO medicines for BP	80 mg

Table 7b : Effect of Adipomimetin on Type-II diabetes as well as hypertension on participants described in Table 7a(S: Systolic; D: Diastolic)

S. No.	Sex	Adipomimetin/ tablet (mg) (3 tablets/ day)	Day 0		Day 15		Day 30		Day 60		Day 90
			Blood Pressure (mm of Hg)
			S	D	S	D	S	D	S	D	S	D
Group 1:Metformin + (in some patients) Voglibose and/or Teneligliptin
1	F	40	150	90	140	80	141	80	140	70	140	80
Group 2. Glymepiride (in most cases or another Sulphonyl Urea in some cases) + Metformin + in some cases Voglibose without or with Teneligliptin
2	M	80	130	90	110	70	110	70	115	75	120	80
3	F	40	150	90	135	85	120	80	120	80	130	70
4	F	40	170	100	140	80	130	80	130	80	120	80
5	F	80	130	76	130	90	130	80	130	80	120	80
6	M	40	130	90	130	80	130	70	130	80	130	80
7	F	80	130	80	120	70	130	80	110	80	130	80
8	F	40	150	90	150	80	140	80	140	90	114	70
Group 3: Only Adipomimetin tablets, no “Standard-of-Care” treatment of Medicines
9	M	40	170	100	140	80	130	80	130	80	120	80
10	M	80	150	80	140	80	130	80	130	70	120	80

Table 8: Effect of Adipomimetin on body weight

Standard of Care treatment: Stabilized since 3 months prior to recruitment	Body weight (kg)
	Day 0	Day 15	Day 30	Day 60	Day 90
Group 1:Metformin + (in some patients) Voglibose and/or Teneligliptin + Adipomimetin (80mg or 40mg three times a day)	71.9	71.9	71.2*	71.4	70.7**
Group 2: Sulphonyl Urea (Glymepiride or any other) + Metformin + occasionally Voglibose without or with Teneligliptin + + Adipomimetin (80mg or 40mg three times a day)	67.4	67.1	67.4	65.9**	65.0**
Group 3: Only Adipomimetin tablets, no “Standard-of-Care” treatment of Medicines + Adipomimetin (80mg or 40mg three times a day)	76.2	75.8	75.5*	74.8**	74.7**
Pooled means
Pooled data 80mg+40 mg	69.8	69.6	69.5	68.6**	67.9**
Pooled data 80mg	67	66.8	66.5	66.4	64.8**
Pooled data 40mg	71.8	71.5	71.6	70.1**	70.0**
Pooled data Male	75.8	75.4	75.2	74.4**	74.0**
Pooled data Female	67	66.9	66.9	65.9**	65.0**
Critical Difference
P=0.05	0.56
P=0.01	0.75

Table 9: Effect of Adipomimetin on basal metabolic index/ Body mass index–

Standard of Care treatment: Stabilized since 3 months prior to recruitment	BMI
	Day 0	Day 15	Day 30	Day 60	Day 90
Group 1:Metformin + (in some patients) Voglibose and/or Teneligliptin + Adipomimetin (80mg or 40mg three times a day)	30.02	30.1	30.02**	30.12**	30.12**
Group 2: Sulphonyl Urea (Glymepiride or any other) + Metformin + occasionally Voglibose without or with Teneligliptin + + Adipomimetin (80mg or 40mg three times a day)	27.7	27.6	27.7	27.1	26.9**
Group 3: Only Adipomimetin tablets, no “Standard-of-Care” treatment of Medicines + Adipomimetin (80mg or 40mg three times a day)	28.6	28.5	28.4	28.1*	28.1*
Pooled means
Pooled data 80mg+40 mg	28.4	28.3	28.3	27.9*	27.7**
Pooled data 80mg	27.6	27.5	27.4	27.3	27.0**
Pooled data 40mg	28.9	28.8	28.9	28.3**	28.2**
Pooled data Male	28.1	28.2	28	27.4**	26.7**
Pooled data Female	28.5	28.4	28.4	28.0*	27.8*
Critical Difference
P=0.05	0.32
P=0.01	0.42

Table 10: Effect of Adipomimetin on pulse rate

Standard of Care treatment: Stabilized since 3 months prior to recruitment	BMI
	Day 0	Day 15	Day 30	Day 60	Day 90
Group 1:Metformin + (in some patients) Voglibose and/or Teneligliptin + Adipomimetin (80mg or 40mg three times a day)	79.3	78.7	76.7*	75.2**	79
Group 2: Sulphonyl Urea (Glymepiride or any other) + Metformin + occasionally Voglibose without or with Teneligliptin + + Adipomimetin (80mg or 40mg three times a day)	78.9	78.5	76.8	76.9	76.2*
Group 3: Only Adipomimetin tablets, no “Standard-of-Care” treatment of Medicines + Adipomimetin (80mg or 40mg three times a day)	84	78.0**	78.7**	77.3**	75.3**
Pooled means
Pooled data 80mg+40 mg	79.7	78.5	77.0*	76.5*	76.8*
Pooled data 80mg	81.3	77.8*	76.7**	76.7**	76.9**
Pooled data 40mg	78.6	78.9	77.2	76.4	76.8
Pooled data Male	80.9	79.4	77.7*	77.7*	79.1
Pooled data Female	79.2	78	76.7	75.9*	75.7*
Critical Difference
P=0.05	2.52
P=0.01	3.34

The results show that amongst 15 clinical parameters of a diabetic patient observed in this trial, which includes clinical parameters related to Type-II diabetes and also of other lifestyle diseases such as hypertension, weight gains, which are suggestive of Metabolic Syndrome (see the summary Table 1 and other tables thereafter), the tables show, without an exception that, wherever the average Day 0 level was clinically abnormal for that parameter, the same has come back to normal or near normal level statistically significantly; and wherever the average Day 0 observation was already within normal range, it remained within normal limits on Day 90 also and difference between means of 0 day and 90^th day was either statistically insignificant or the Day 90 level was within normal limits. The effect of bringing back nearer to homeostasis for more than one lifestyle disease-indicating clinical parameter is possible only if the action of the cause is Adiponectin itself or if it is not Adiponectin, it is mimetic of Adiponectin. Hence, the Investigational Product, which is the composition comprising heat stable plant juice soluble plant protein obtained as a water insoluble concentrated mass, essentially free from components more soluble in the plant juice, and enriched in heat stable proteins of the plant juice is an agonist/mimetic of Adiponectin. The water insoluble mass is named as “Adipomimetin”. This mimetic action is not present in any of the known medicines; and this fact makes Adipomimetin an outstanding product as First Line response for all lifestyle diseases/disorders caused by deficiency of Adiponectin.

The observations given in tables 2 to 10 show that both 80 mg tablets as well as 40 mg tablets were efficacious and there were no statistical differences between their efficacies on any clinical parameter. Hence, conclusion is that 40mg tablets should be used in preference to 80mg tablets.

Achieving homeostasis levels is seeninAdipomimetinadministration as add-on to State-of-Art treatment and achievement of homeostasis is seen also to the same extent even in Adipomimetinas stand-alone administration in Group 3.These results show that action of Adipomimetin does not have to be administered as “add-on” to Standard-of-care therapiesto be effective, but stands on its own feet and is capable of producing desired results with as well as without standard-of-care treatment.

Because each lifestyle disease arising from deficiency of Adiponectin has different symptom, each symptom requires a different medicine.With further degeneration of Type-II diabetes, the dosage of and number of medicines required to be administered increases, and it is very common to end up with large number of dosages of different medicines per day that are required to be consumed; and whereas presuming that it is this that helps to add to number of years to the life, the quality of life deteriorates significantly due to increasing severity of side effects and interactions of multiple medicines. Until Adiponectin is above the minimum threshold requirement, none of these medicines are required because Adiponectin is credited to have properties of decreased gluconeogenesis, increased glucose uptake, (lipid catabolism, β-oxidation. triglyceride clearance protection from endothelial dysfunction (important facet of atherosclerotic formation), insulin sensitivity, weight loss. control of energy metabolism., up-regulation of uncoupling proteins and reduction of TNF-alpha.

For those who have risk factors of getting lifestyle diseases, such as those who are on the verge of crossing Body Mass Index of 24 or have genetic risk factor, Adipomimetin provides an opportunity to explore its consumption as a means to substantially delay onset of the lifestyle diseases or disorders.

For those who are diagnosed for the first time with Type-II diabetes only or Type-II diabetes as well as hypertension (Group 3), Adipomimetin provides an opportunity to sgart its consumption immediately and return to almost homeostasis so that necessity for chemical anti-diabetics and anti-diabetics as well as anti-hypertensive medicines may arise very much late or, possibly, not at all too.

For those who already are on medicines for such lifestyle diseases, Adipomimetin provides an opportunity to start its administration as add-on to State-of-Art therapy; and if clinical parameters show significant improvement, to stepwise withdraw the medicines.

If one lifestyle disease develops it may follow with other lifestyle disease/s or disorder/s also, such as hypertension and secondary diseases arising from them such as hyperlipidemia, atherosclerosis each of which is progressively degenerative.Secondary diseases may also develop from the lifestyle diseases such as Chronic Kidney Disease, various types of neuropathies, atherosclerosis, chronic fatigue syndrome, obesity and like diseases finally culminating in heart disease or stroke. Each different symptom of these different diseases/disorders need different medicine and as the diseases degenerate further, need additional medicines in combination. It is well known that life gets additional years by medicine use, but quality of that life also progressively degenerates due to side effects and interactions of these medicines. If medicines cannot be totally avoided, it is also a big relief if their requirement could be postponed or reduced on number and dosages as much as possible, progression of diseases can be slowed down considerably and quality of life could be preserved to a significant extent.

This is potentially possible by using Adipomimetin since it is a single product that acts on the root of all lifestyle diseases that arise from deficiency of Adiponectin and is useful as First Line response to lifestyle diseases/disorders before their manifestation and also after their first appearance.

Body weight approaching Body Mass Index of 24 may be regarded as indication that Adiponectin level is coming down closer to the minimum threshold. That could be the time to start consuming Adipomimetin; which is a safe food supplement because it is derived from usually consumed Dark Green Leafy Vegetables. This is reasonably expected to substantially delay manifestation of any lifestyle disease.

Each lifestyle diseaseis progressively degenerative,has a different symptom, each symptom needs a different medicine, and in course of time needs higher dosages of same and also other combinations of medicines. Hence, in an approach of responding to the lifestyle diseases with medicines, one starts with a single medicine to start with. However, as the disease goes on progressive degeneration and other lifestyle diseases and secondary line of diseases arise on account of the primary lifestyle disease, it eventually leads to several symptoms, equally increasing number of medicines required to be consumed. It is well known that each medicine has its own side effects and multiple medicines result in additional side effects due to their mutual interactions. Deficiency of Adiponectin is a single cause that gives rise to above diverse symptoms each requiring separate medicine to control within acceptable limits because a medicine is symptom-specific and symptom of each of above list of lifestyle diseases is different; only Adiponectin, and no medicine, has mechanism of action to control all of them simultaneously. It is for the first time that a practically feasible mimetic of Adiponectin has been made available in the form of the Adipomimetin. Balancing so many diverse clinical parameters of lifestyle diseases through only one single mode of action is possible only through activating AMP-activated protein kinase (AMPK) pathway, the energy sensor of cells, which mediates balancing acts that maintain homeostasis of all metabolic pathways that keep clinical parameters related to lifestyle diseases within normal range. It is this pathway which is activated by Adiponectin as per the metabolic requirements of the body. Thus, Adiponectin distinguishes itself as having only one function; maintaining homeostasis through activating AMPK pathway. Hence, when Adiponectin level in the body is higher than a threshold level, the result is accurate maintenance of homeostasis of the clinical parameters of above list of lifestyle diseases; no known medicine has this property. When Adiponectin becomes deficient, unless this deficiency is made up, above list of clinical parameters become abnormal and produce disease typical to itself; and for each of them a separate medicine is required. At present, above results have confirmed that when Adiponectin becomes deficient, Adipomimetin supplements the same forits function, bringing back the clinical parameters from abnormal level to closer to normal level by performing same function.Adipomimetin is the only product available currently that can be manufactured at practically relevant scale for supply in the market enough to satisfy the demand of victims of lifestyle diseases, which is capable of supplementing Adiponectin for same mechanism of action. Whether Adipomimetin would restore the level of homeostasis to original level, i.e. fully normal level, would depend on how much of the damage caused by the disease to the metabolism/body systems has become irreversible prior to its administration.Action of medicines known so far is dose dependent and not responsive to status of homeostasis.

It may be noted that State-of-Art treatmentsof the patients enrolled were stabilized as optimumat least for three months prior to their enrollment in the clinical trial; and in most cases the clinical parameters were more or less in abnormal range. This indicated the limitation of the State-of-Art treatment, which was different to each individual. Yet after start of administration of Adipomimetin, unless the clinical parameter was already in normal range on Day 0, in all cases, there was a rapid improvement in the direction of original homeostasis level. Thus, the point to note is that no State-of-Art treatment was able to cover full potential of recovery. Thus, the scope of improvement in clinical condition that was not possible to be covered by State-of-Arttreatment wasalso covered by Adipomimetin. Thus, Adipomimetin brought back the enrolled patients closer to normal, who had different levels of intensity of Type-2 diabetes with respect to abnormality in clinical parameters. With respect to blood sugar levels, they came back at least within a pre-diabetic level. This effect has been seen in the Group 1 and 2 on medicines and also in Group 3 on no medicine. This result on Group 3 shows that in absence of State-of-Art treatmentalso, Adipomimetin is able onstand-alone administration to bring a diabetic state to pre-diabetic state. This is exactly what Adiponectin would do when it is available in critical quantity in blood.

This clearly indicates that Adipomimetin should be the most rational choice for First Line response to every first-time diagnosis of above lifestyle diseases; and only that much of medicines would be prescribed which are requiredfor treating residual symptomsafter administering Adipomimetin.

This also shows that it is possible to envisage for persons already on medicines,to partly or fully replace the medicines, depending on the level of Adiponectin deficiency, by administering Adipomimetin as an add-on to state-of art treatment to begin with, monitoring the clinical parameters as they move closer to pre-diabetic stage or lower than pre-diabetic stage and slowly withdrawing the medicines. In the process, there may be some rise in clinical parameters to abnormal level, however, if after complete withdrawal, the final level stabilizes to below or very close to pre-diabetic level,that could be a desirable outcome.

These results provide support to a documented case study¹³in which a total replacement of 500mg Metformin three times a day was done by Adipomimetin within a span of three weeks.In this instance, it was observed thatthe add-on consumption resulted in sharp decline in post-prandinal blood glucose after first dose itself; which is profoundly surprising given the fact that Adipomimetin is a water insoluble concentrate of nutrients derived from plant juice and no other anti-diabetic product except Insulin and no plant derived product is known to give sucba sharp decline in post-prandinal blood sugar. this was followed by slow increase in fasting and post-prandinal sugar by the time last of the Metformin tablet was discontinued at the end of 3^rdweek;however, that increased level was also within the pre-diabetic level whichwas much below the level of Fasting and Post-prandinal blood sugar when the human subject was on Metformin alone; and this level was maintained for about 11 months after complete replacement of Metformin by Adipomimetin. Replacement of Metformin was accompanied by sharp reduction in chronic fatigue and reduction in hypertension. These observations are confirmed in this clinical trial.

However, in case pre-diabetic levels are not achieved by total replacement, achieving as much reduced dose of medicines as possible to maintain clinical parameters just near the pre-diabetic range could be the next desirable choice. Even whatever is the reduction in quantity of medicines achieved by administration of Adipomimetin is a matter of great relief, since above listed lifestyle diseases are progressively degenerative, they require lifelong consumption of multiple medicines in ever increasing dosage and increasing costs and of increasing side effects which leads to chronic fatigue in course of time accompanied by progressive loss of quality of life. Exclusive use of medicines does have provided longevity but with highly reduced quality of life. Adiopomimetin as first line response to lifestyle diseases followed by medicines only to the extent of controlling residual symptoms has potential to ensure preserving quality of life to large extent to the longevity achieved.

In 90days trial, average BMI did come down significantly at P=0.01, which was still declining. However, on Day 90 average BMI was still above the limit of 24.9, hence, considered as overweight. BMI of 24.9 at average height of 1.57 meters will require a body weight of = (1.57*1.57)*24.9= 61.4kg. Thus, a decline of average weight of67.9 to 61.4 kg i.e. = 6.5kg will be required to restore average BMI to normal level. In 90 days, there has been a statistically significant decline from 69.8-67.9 = 1.9 kg. Presuming same rate of decline in weight, a further decline in weight of 6.5 kg shall require 307 days. This is very much consistent with the usual rate of putting weight to cross the limit of BMI of 24.9 when homeostasis gets disturbed. It is clear that the restoration of homeostasis with respect to body weight mediated through AMPK pathway shall also be by same rate at which the weight was put up; and that may actually be safest rate of decline in BMI.

However, the rate of drop in weight was observed to be more rapid within 90 days in a morbid obese individualwhose BMI as 40.89, and Day 0 weight was 92kg and Day 90 weight was 86kg. For lesser BMI, the rate of lowering of body weight was lower. Thus, here too, the mechanism of action is consistent to reestablishment of homeostasis; and the rate of reestablishment shall be relative to the quantum of difference of the abnormallevel of the clinical parameter from the normal/homeostatic level.

Since Adipomimetin seems to be capable of restoring homeostasis to much near its original status, which is not possible by any other currently available anti-diabetic products, there is a reasonable potential in it to either stop progression of the pathological clinical symptoms or at least slow its progressive degeneration substantially.

Thus, the product named as Adipomimetin in this paper, which is made from green leafy vegetable Trigonellafoenum-graecum L. (Methi; Fenugreek) is proven to have Adiponectin Agonist properties. Tablets containing 40mg Adipomimetinthree times a day seems to be the dose of choice for getting acceptable level of efficacy. This can also be potentially made from any other reasonably edible green leafy vegetation/vegetable. The dosage form is a concentrate of several heat stable ingredients of Methi juice, including heat stable proteins,and the product is named as “Adipomimetin”. The process of making the same is a simple process scalable by bioprocess engineering methods¹³. This product is likely to change the strategies of handling Type-2 Diabetes, hypertension, hyperlipidemia, hypertriglyceridemia, obesity and all consequences of Metabolic Syndrome that leads to heart disease and a number of secondary consequences such as Chronic Kidney Disease, neuropathy etc.Metabolic Syndrome is believed to be one of the causes of even Polycystic Ovary Syndrome, which is emerging as one of the major concerns in women between age group of 16-44.

1. Bailey CJ, Tahrani AA, Barnett AH. Future glucose-lowering drugs for type 2 diabetes. Lancet Diabetes Endocrinol. 2016;4(4):350-359. doi:10.1016/S2213-8587(15)00462-3

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10. Yun DJ, Zhao Y, Pardo JM, et al. Stress proteins on the yeast cell surface determine resistance to osmotin, a plant antifungal protein. Proc Natl Acad Sci U S A. 1997;94(13):7082-7087. http://www.ncbi.nlm.nih.gov/pubmed/9192695. Accessed December 13, 2018.

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https://arastirmax.com/en/system/files/dergiler/160852/makaleler/2/2/arastrmx_160852_2_pp_196-207.pdf

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Acknowledgement:

We thank statistician Dr. S.G. Bhogle, Retd. Professor & Head, Faculty of Social Sciences, Water And Land Management Institute (WALMI), Aurangabad, Maharashtra, India for his examining the statistical validity of sample size and on standards used in this publication for statistical analysis and interpretations.

Conflict of interest: VAS and CVS are patentee of this product and rest of authors declare no conflict of interest.

Funding

The present study was funded by PhytabolitesNutraceuticalsPvt.Ltd. Funders are licensee of patent application on Adipomimetin.

Ethical approval

A clinical trial of tables made from the batch 7F on Type II diabetes patients was arranged at AyurvedaRugnalaya and Sterling Multi-specialty Hospital Nigdi,Pune with due approval from the institutional ethics committee (CTRI/2017/08/009282). The composition comprising heat stable plant juice soluble plant protein obtained as essentially a water insoluble concentrated mass free from components more soluble in the plant juice, and enriched in heat stable proteins of the plant juice, being a mimetic of Adiponectin, has been named as “Adipomimetin”.

Composition of tablets

Composition of 500mg tablet containing 40 mg Adipomimetin

Constituents	Weight (mg)
Adipomimetin	40
Whey protein	300
Lactose	60
Microcrystalline Cellulose	89.25
Povidone K30	7.5
Magnesium Stearate	2
Colloidal silicon oxide	1.25
Total weight of tablet	500

Composition of 500 mg tablet containing 80 mg Adipomimetin

Constituents	Weight (mg)
Adipomimetin	80
Whey protein concentrate	260
Lactose	60
Microcrystalline Cellulose	89.25
Povidone K30	7.5
Magnesium Stearate	2
Colloidal silicon oxide	1.25
Total weight of tablet	500

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A food supplement having Adiponectin Agonist properties

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Abstract

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