Screening of active ingredients in Kaixin Powder for Alzheimer’s disease based on molecular docking

doi:10.21203/rs.3.rs-1892456/v1

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Screening of active ingredients in Kaixin Powder for Alzheimer’s disease based on molecular docking

https://doi.org/10.21203/rs.3.rs-1892456/v1

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Objective

Using molecular docking technique, some active ingredients in Kaixin Powder would be sorted based on the three-dimensional structures of key targets of Alzheimer’s disease.

Methods

The ingredients of Kaixin Powder were obtained by searching relevant literatures. The targets of Alzheimer’s disease were searched from databases like GeneCards, DisGeNET, NCBI, UniProt and KEGG. The core targets of Alzheimer’s disease were obtained by intersection of the above databases. Molecular docking was performed using AutoDock Vina software to explore the affinity and binding modes between candidate ingredients with the core targets.

Results

The results showed that 112 structures were detected from Kaixin Powder and the ingredients mainly belonged to ginsenosides, polygala saponins, xanthones, oligosaccharide esters and Poria triterpenoids. Eleven targets close to Alzheimer’s disease were summarized from the databases. The combining capacity of active ingredients with APP and MAPT was worse and that with PTGS2, BACE1, ACHE and NMDA was better.

Conclusion

With the characteristics of multi-component and multi-target, there is a component-target-pathway crosstalk in the anti-AD effect and nervous system protection of Kaixin Powder. Molecular docking technique to mine active ingredients is used to facilitate the discovery of novel anti-AD and lead compounds from Chinese herbal medicines.

Kaixin Powder

Alzheimer’s disease

molecular docking

ginsenosides

polygala

Poria

calamus

Alzheimer's disease (AD) is a progressive neurodegenerative disease with the characteristics of insidious onset, which often occurs in the elderly. More than 55 million people all over the world are currently living with dementia, and WHO estimates that there will be more than 100 million by 2050 ¹. Clinical features of patients include memory and cognitive impairment, decreased language skills, personality, and behavioral changes. The etiology of AD is still unknown. According to existing hypotheses, many abnormal physiological and biochemical reactions play an important role in the pathogenesis of AD, for example, cholinergic neuron hypothesis, Aβ toxicity hypothesis, Tau protein hypothesis, inflammation hypothesis, insulin hypothesis, free radical damage hypothesis, metal ion disorder hypothesis, etc. ^2–3 Currently, FDA-approved drugs for the treatment of AD include acetylcholinesterase inhibitors (AchI) tacrine, donepezil, galantamine, rivastigmine and N-methyl-D-aspartic acid (NMDA) receptor antagonist memantine. Meanwhile, domestically approved drugs include Huperzine A (a reversible cholinesterase inhibitor), and Mannat sodium capsules, a drug targeting the brain-gut axis ^4–5. Most of the clinical anti-AD drugs have a single target, which can only temporarily relieve the symptoms of patients but cannot block the pathogenesis ⁶. Therefore, anti-AD drugs with multi-targets have become a new strategy for research.

Kaixin Powder originated from Important Formulas Worth a Thousand Gold Pieces for Emergency (Bei Ji Qian Jin Yao Fang) written by Sun Simiao, a Tang Dynasty medical scientist. It is one of the ancient classic prescriptions for nourishing the heart and opening the orifices, invigorating the spleen and soothing the mind, and communicating with the heart and kidney. It can treat the forgetfulness caused by the loss of nourishment of the heart, the phlegm blocking the heart orifices, and the lack of communication between the heart and the kidney. Kaixin Powder, composed of four traditional herbs, Panax ginseng C. A. Meyer, Wolfiporia cocos (F.A. Wolf) Ryvarden & Gilb., Polygala tenuifolia Willd, and Acorus tatarinowii, is commonly used clinically to improve the symptoms of neuropsychiatric diseases such as memory loss, language disorders, cognitive dysfunction, and personality changes. Otherwise, Kaixin Powder has significant curative effect on mild to moderate depression and Alzheimer’s disease ^7–8. There have been many reports on the pharmacology of Kaixin Powder. And modern studies have shown that Kaixin Powder has pharmacological effects such as anti-senile dementia, improvement of learning and memory ability, anti-aging, anti-depression, sedative and soothing, and anti-fatigue ⁹. However, the material basis and mechanism of its action are still not clear. The computer virtual screening technology based on molecular docking technology has the characteristics of high efficiency, rapidity and low cost, and plays a great role in the research of traditional Chinese medicine. In the present study, molecular docking technology was adopted, the potential targets of AD were used as receptors, and the chemical components in Kaixin Powder were used as ligands to screen the material basis of Kaixin Powder against AD, and to provide reference for its further development.

2.1 Chemical Composition of Kaixin Powder

Through literature and database search, a total of 112 components of Kaixin Powder with well-defined structures were obtained (as shown in Supplementary Table 1), including 27 ginsenosides (ginsenosides Rb1, ginsenosides Rg1, ginsenosides Re, etc.), 24 triterpenoid acids from Poria (pachymic acid, tumulosic acid, poricoic acid, 3-dehydrotrametenolic acid, etc.), 19 polygala saponins (tenuifolin, onjisaponin A, polygalasaponin XXI, etc.), 13 polygala xanthones (polygalaxanthone III, sibiricaxanthone A, etc.), 14 polygala oligosaccharide esters (3,6’-dispiroyl sucrose, sibiricose A5, tenuifoliside A, etc.) and 15 volatile oils from calamus (camphor, elemicin, shyobunone, α-asarone, β-asarone, etc.).

2.2 Targets of AD

According to the search characteristics of GeneCards, DisGeNET, NCBI, UniProt and KEGG databases, select the targets most closely related to AD. The search results of the above five databases were intersected, and a total of 10 target proteins were obtained, namely disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), Apolipoprotein E (APOE), amyloid-beta precursor protein (APP), beta-secretase 1 (BACE1), cyclin-dependent-like kinase 5 (CDK5), glycogen synthase kinase-3 beta (GSK3B), microtubule-associated protein tau (MAPT), presenilin 1 (PSEN1), presenilin 2 (PSEN2), and prostaglandin G/H synthase 2 (PTGS2).

Presenilin (PSEN) includes PSEN1 and PSEN2, whose gene mutations can lead to familial AD. The drug targets for AD treatment that have been marketed include ACHE and NMDA. Therefore, eleven target proteins except PSEN2 were selected as receptors for molecular docking with the chemical components in Kaixin Powder. The relevant information of each target protein is shown in Table 1.

2.3 Binding analysis of chemical constituents and targets

By using AutoDock Vina software, 112 chemicals and 11 target proteins in Kaixin Powder were docked (as shown in Supplementary Table 2). Among the listed drugs, the binding energy of AchIs and ACHE were (-8.9~-7.0) kcal/mol, and the binding energy of memantine and NMDA was -6.2 kcal/mol. It is generally believed that the lower the energy when the ligand-receptor binding conformation is stable, the greater the possibility of the effect. Binding energy ≤–1.2 kcal/mol was used as the screening standard. And when the binding energy was ≤–5.0 kcal/mol or ≤–7.0 kcal/mol, it was considered that the component had good or strong binding ability to one target ¹⁷. According to the present experimental results, the binding ability of Kaixin Powder to APP and MAPT was significantly lower than that of other target proteins, and the binding ability to PTGS2, BACE1, ACHE and NMDA was the best. Among the interactions with binding energy ≤–7.0 kcal/mol, 15 components could bind to 9 target proteins; among the interactions with binding energy ≤–9.0 kcal/mol, there are still 20 components that could bind to 3 or more target proteins were bound. The results were shown in Table 2.

2.4 Interaction analysis for positive results.

The five results with the lowest binding energies of Kaixin Powder components to PTGS2, BACE1, ACHE and NMDA were analyzed, and the results were shown in Table 3. Trp286, Phe295, Arg296, and Tyr341 were the key residues in the interaction between AchI and ACHE. The docking sites of sibiricaxanthone A and tumulosic acid were similar to each other and their binding ability was stronger than those of the marketed AchIs. Gln73 and Tyr71 of BACE1 were the key binding sites of polygala saponins and xanthones. Memantine could form a hydrogen bond with the 48th proline of the NR1 subunit of the NMDA receptor. Due to their large molecular weight, the active ingredients of Kaixin Powder mostly fell into the “pocket” of the NMDA receptor, interacting with the amino acid residues in NR2 subunit. The amino acid residues Asn34, His39, and Pro153 of PTGS2 were the main binding sites of components in polygala. The components with the lowest binding energy to each target were selected, and their binding modes and interactions were observed. The results were shown in Figure 1.

3.1 Chemical composition of Kaixin Powder and AD.

Kaixin Powder is the basic traditional formula in China for AD treatment, which can inhibit the activity of ACHE in the brain, reduce the content of MAPT, inhibit the production of Aβ, reduce neuronal damage, and exert anti-AD effects through various pathways ^11-12. The 112 chemical components collected in this experiment include ginsenosides, triterpenoid acids from Poria, polygala saponins, polygala xanthones, polygala oligosaccharide esters, and volatile oils from calamus. These components are specific to traditional Chinese medicine and can play a role by entering the bloodstream, and are important quality control components of Kaixin Powder ¹³. Ginsenosides have significant regulatory effects on the nervous system, including neuroprotective action, antidepressant, and improving cognition, learning and memory. Ginsenoside Rb1 is the first major saponin monomer found to protect ischemic brain injury. It has the function of enhancing the cholinergic system, and can play a nootropic, nerve damage repair, and cerebral ischemia protective effect in the central nervous system ^14-15. Ginsenoside Rg1 can exert neuroprotective effects by inhibiting inflammatory factors and inhibiting neuronal apoptosis. Poria triterpenoids have nootropic effects, can improve spatial memory impairment, and reduce the toxicity of Aβ to nerve cells. pachymic acid is the most abundant triterpenoid in Poria, and has sedative, hypnotic, and antioxidant effects ¹⁶. Polygala saponins, xanthones, and oligosaccharide esters, as the specific ingredients in Polygala L., have neuroprotective effects. For example, tenuifolin can inhibit BACE1 activity and reduce Aβ production, reducing Aβ-induced oxidative stress damage and inflammatory responses¹⁷. 3,6′ -Di-spinacyl sucrose can produce antidepressant effects by affecting neural plasticity, neural differentiation, and cellular oxidative stress ¹⁸. Xanthones have biological activities such as central excitation and antitumor. Volatile oils in calamus have high lipid solubility and can quickly enter the brain tissue through the blood-brain barrier to exert neuroprotective effects ¹⁹.

3.2 Clinical application and development progress of anti-AD drugs

Tacrine was the first drug approved by the US FDA to treat AD. But it has been gradually replaced by other drugs due to its high liver toxicity. Donepezil can improve the cognitive ability and daily living ability of patients with mild and moderate AD by inhibiting ACHE and increasing the content of central ACH, and it is well tolerated ²⁰. Rivastigmine (also known as rivastigmine) oral preparations and transdermal patches can be used in AD, and its clinical application scale is expanding. Galantamine can effectively delay the deterioration of cognitive function and is still effective when donepezil is ineffective or intolerable ²¹. Huperzine A is an AchI developed by Chinese scholars to improve cognition and memory ²². Memantine, as a noncompetitive NMDA receptor antagonist with low-moderate affinity and voltage-dependent properties, is approved for moderate to severe dementia ^23-24. In addition, the FDA approved a combination of memantine hydrochloride extended-release (XR) and donepezil hydrochloride for the treatment of moderate-to-severe AD.

In 2019, Sodium Oligomannate Capsule (also named GV-971), a drug to treat mild to moderate Alzheimer’s disease based on targeting the brain-gut axis, was approved for marketing through the priority review and approval process to improve cognitive function in patients ⁴. Now it is undergoing an international multi-center Phase III clinical trial. In 2020, Tauvid received FDA approval for positron emission tomography imaging of the brain to assess the density and distribution of aggregated tau neurofibrillary tangles in the brain ²⁵. In 2021, FDA approved aducanumab, a new anti-AD drug jointly developed by Biogen of the US and Eisai of Japan, under the accelerated approval channel. Aducanumab is a monoclonal antibody targeting β-amyloid protein (Aβ) that selectively binds to amyloid deposits in the brain of patients, reducing the accumulation of β-amyloid, and thereby slowing disease progression ²⁶.

3.3 Targets of AD

AD is a cranial nerve disease with two main symptoms: one is Aβ formed by the hydrolysis of APP, which is abnormally deposited outside neurons to produce strong neurotoxic effects; the other is neurofibrillary tangles formed by abnormal phosphorylation of MAPT ^27-28. APOE is involved in lipid metabolism and cholesterol metabolism in vivo. High expression of APOE and its receptors can promote the clearance of Aβ in the brain of patients, improve cholesterol transport, protect synapses and prevent inflammatory responses ^29-30. GSK-3β is overactive in the brains of AD patients. By inhibiting GSK-3β, the neurotoxic effects of Aβ and MAPT can be effectively reduced ^31-32. BACE1 is a key rate-limiting enzyme in the formation of Aβ ³³. Gamma-secretase (6LR4), an intramembrane protease complex composed of four subunits of presenilin 1 (PSEN1), Pen-2, APH-1A and Nicastrin, is mainly involved in the cleavage and hydrolysis of transmembrane proteins such as APP and Notch ³⁴.

NMDA receptors not only play an important physiological role in the development of the nervous system, but overactivated or overinhibited receptors are closely related to a series of neurological and psychiatric diseases ^35-36. The metalloprotease ADAM10 is implicated in neurodegeneration, cancer and inflammation. ADAM10 is involved in the developmental processes of the nervous system, including cell proliferation, migration, differentiation, survival, axonal growth and myelination ^37-38. CDK5 is also closely related to the pathogenesis of AD. It can slow down the pathological process of AD by reducing Aβ deposition, slowing the formation of NFTs caused by hyperphosphorylation of MAPT, maintaining synaptic plasticity, and inhibiting neuronal apoptosis ^39-40. According to the inflammatory hypothesis, neuroinflammation and Aβ extensively cause brain damage and cognitive impairment. Non-steroidal anti-inflammatory drugs (NSAIDs) can regulate the activity of gamma-secretase and play a role in delaying the progression of AD to a certain extent ^41-42.

3.4 Results of molecular docking

In this study, the binding energy of 25 components in Kaixin Powder to ACHE was lower than that of tacrine (-8.9 kcal/mol), including 9 triterpenoid acids from Poria, 7 polygala xanthones, 5 polygala saponins, such as tumulosic acid, eburicoic acid, sibiricaxanthone A, and polygalasaponin XXII. The docking sites of polygala xanthones with ACHE are similar to the listed AchIs, which means these ingredients has a promise for new effective drugs. Most of the components of Kaixin Powder can well fall into the "pocket" of NMDA receptor due to their large molecular weight, so the binding effect is much better than that of memantine.

The binding ability of components in Kaixin Powder with APP and MAPT was significantly lower than that of other target proteins, and the binding ability with PTGS2, BACE1, ACHE and NMDA was the best, suggesting that Kaixin Powder may have no direct effect on β-amyloid precursor protein and MAPT. Kaixin Powder may exert anti-AD effects via inhibiting cyclooxygenase, cholinesterase, β-secretase, and NMDA receptors. Among the 21 positive results docked with the above 4 target proteins, the components of Kaixin Powder include: ginsenosides (ginsenoside Rb3, malonyl-ginsenoside Rc), xanthones (polygalaxanthone III, polygalaxanthone V, polygalaxanthone VIII, sibiricaxanthone A, sibiricaxanthone F, and lancerin), polygala saponins (onjisaponin E, onjisaponin Z, senegin III, polygalasaponin XXI, polygalasaponin XXXI, polygalasaponin XXXV, and senegasaponin A), oligosaccharide esters (arillanin A), and triterpenoid acids (3beta-p-hydroxybenzoyldehydrotumulosic acid and tumulosic acid). The binding energies of these positive results were all <-9.0 kcal/mol.

The computer virtual screening technology by molecular docking is an important method to screen new drugs based on the action target, which plays a critical role in elucidating the mechanism and the targets of people and in new drugs discovery and development ⁴³. Six active components with New Delhi metallo-β-lactamase (NDM-1, B1 class) inhibitory activity were obtained using molecular docking and three of them were finally confirmed through in vitro experiments ⁴⁴. This effectively reduces screening and troubleshooting time, and greatly improves screening efficiency. AutoDock Vina is a molecular docking software developed by the Molecular Graphics laboratory and is widely used due to its high accuracy and speed ⁴⁵.

Kaixin Powder can increase the content of cholinesterase in the brain tissue of AD model animals, and improve the learning and memory ability of animals ⁴⁶. In clinical application, Kaixin Powder combined with Donepezil Hydrochloride Tablets can significantly improve the total effective rate of AD ⁴⁷. According to the research, this paper uses molecular docking technology to screen the chemical components of Kaixin Powder according to 11 AD-related target proteins. We finally obtain compounds with good binding ability to AD target proteins, including ginsenosides, polygala saponins, xanthones, oligosaccharide esters and Poria triterpenoid acids. The volatile oils from calamus may play a role in guiding meridians in Kaixin Powder because of their high fat solubility and easy to pass through the blood-brain barrier. With the characteristics of multi-component and multi-target, there is a component-target-pathway crosstalk in the anti-AD effect and nervous system protection of Kaixin Powder. The anti-AD activity of these components needs to be verified by further biological experiments.

4.1 Collection and preparation of ligand molecules

Search literatures and databases related to the chemical constituents of Kaixin Powder, and collect relevant constituents. The 3D structures of Kaixin Powder ingredients and marketed drug ingredients were obtained from Pubchem (https://pubchem.ncbi.nlm.nih.gov/). Use OpenBabel software to convert them into mol2 format files. Autodock Tools software was performed to minimize the energy of the component structure, determine the Root of the component, select the twistable bond. Finally, the files were saved in *pdbqt format.

4.2 Screening and preparation of receptor proteins.

In order to comprehensively and accurately screen AD target proteins, the search term “Alzheimer's disease” was used in GeneCards (https://www.genecards.org/), DisGeNET (https://www.disgenet.org/), NCBI (https://www.ncbi.nlm.nih.gov/), UniProt (https://www.uniprot.org/) and KEGG (https://www.kegg.jp/) databases ^48-51. The search results of each database were taken intersection. Combined with the results of the literature search, we obtained AD-related target proteins.

4.3 Molecular docking

The 3D structures of the above target proteins were searched and downloaded from the RCSB protein data bank ⁵². Autodock Tool software was used to process the protein structure: removing solvent molecules and ligand molecules, hydrogenating protein molecules, assigning atom types, and saving them as * pdbqt format files ⁵³. Molecular docking was performed using AutoDock Vina software, and the docking of ligands and proteins was analyzed and observed using PyMOL and Discovery Studio software ⁵⁴.

Author Contributions

GC and QF performed the study. GC and WL integrated the data and wrote the paper. HL and CS prepared the figures. All authors contributed to the article and approved the submitted version. JY and QF conceptualized and designed the experimental plan. All authors contributed to the article and approved the submitted version.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

This work was supported by the Shandong Provincial Natural Science Foundation (No. ZR2021QH289), and Shandong Major Scientific and Technological Innovation Project (No. 2021CXGC010508).

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Table 1 Core targets of AD
Gene	Protein	chromosome	UniProt	PDB ID
ACHE	acetylcholinesterase	7	P22303	1f8u
ADAM10	disintegrin and metalloproteinase domain-containing protein 10	15	O14672	6be6
APOE	apolipoprotein E	19	P02649	6nco
APP	amyloid-beta precursor protein	21	P05067	2wk3
BACE1	beta-secretase 1	11	P56817	4rcd
CDK5	cyclin-dependent-like kinase 5	7	Q00535	4au8
GSK3B	glycogen synthase kinase-3 beta	3	P49841	6h0u
MAPT	microtubule-associated protein tau	17	P10636	6nwp
NMDA	N-methyl-D-aspartic acid	9	Q05586	5h8q
PSEN1	presenilin 1	14	P49768	7d8x
PTGS2	prostaglandin G/H synthase 2	1	P35354	5kir

Tab. 2 Results of molecular docking between ingredients of Kaixin Powder and AD targets
Gene	n1(≤–5.0 kcal/mol)	Affinity of n1 (kcal/mol)	n2(≤–7.0 kcal/mol)	Affinity of n2 (kcal/mol)
ACHE	112	-8.13±0.94	100	-8.34±0.68
ADAM10	112	-7.87±1.10	94	-8.23±0.74
APOE	111	-6.40±0.57	19	-7.26±0.27
APP	60	-5.45±0.32	0	—
BACE1	111	-8.06±1.07	98	-8.37±0.67
CDK5	111	-7.13±0.79	71	-7.58±0.47
GSK3B	108	-7.75±0.96	93	-8.03±0.66
MAPT	84	-5.84±0.48	1	-7.0
NMDA	112	-7.97±1.12	94	-8.34±0.78
PSEN1	107	-7.65±1.02	78	-8.14±0.66
PTGS2	112	-8.41±1.17	100	-8.70±0.85

Tab. 3 Interactions of ingredients of Kaixin Powder with ACHE, BACE1, NMDA and PTGS2
gene	ingredients /PubChem CID	Affinity (kcal/mol)	hydrogen bond	hydrophobic interaction
ACHE	3beta-p-hydroxybenzoyldehydrotumulosic acid /15391339	-10.2	Tyr341	Tyr72、Tyr124、Trp286、Phe297、Tyr337、Phe338、Tyr341
	sibiricaxanthone A /21581292	-10.1	2[Trp286]、Phe295、Arg296、Tyr337、Tyr341	Tyr124、Trp286、Leu289、Tyr341
	lancerin /5281645	-9.8	Tyr124、2[Ser293]	Trp286、Tyr341
	senegasaponin A /71627223	-9.7	Thr75、Gly121、Ser203、Asn283、Glu289、Glu292、Ser293、Phe295	Tyr124、Trp286、Phe338、Tyr341
	tumulosic acid /12314446	-9.5	Ser293、Phe295、2[Arg296]、Tyr341	Tyr124、Trp286、Tyr337、Phe338、Tyr341
	tacrine /1935	-8.9	Asp74	Trp286、Phe338、Tyr341
	donepezil /3152	-8.7	Phe295、Arg296	Trp286、His287
	galantamine /9651	-7.9	Arg296	Trp286、Leu289
	huperzine A /449069	-7.4	—	Leu76、Trp286、Tyr341
	rivastigmine /77991	-7.0	Phe295、Arg296	Tyr72、Tyr124、Trp286、Tyr341
BACE1	onjisaponin E /21669943	-10.0	Gln12、Gln73、Asn111、Thr231、Arg235、Lys321、Ser325、Gln326	Tyr71、Phe108、Trp115
	polygalasaponin XXXI /10701737	-9.9	2[Gln73]、Lys107、Thr231、Arg235	Tyr71
	sibiricaxanthone F /54575712	-9.8	Gln73、Trp76	Asp32、Tyr71
	polygalaxanthone V /11968846	-9.7	Thr72、Gln73、Trp76	Asp32、Tyr71
	sibiricaxanthone A /21581292	-9.6	Gly11、Gln12、Gln73、Lys107、Gly230	Asp32、Tyr71
NMDA	polygalasaponin XXXV /102600403	-10.0	A：Glu132、2[Asn219]、Leu279、2[Gly281]、Cys283 B：Lys143、Tyr144、Glu230、Arg248	A: Tyr237
	ginsenoside Rb3 /12912363	-9.9	A：2[Glu132]、2[Glu275] B：His273、Arg287	A: Tyr237 B: Tyr144
	senegin III /21669942	-9.8	A：Glu132、Glu272、Thr241 B：Tyr144、Arg287	B: Tyr144
	senegasaponin A /71627223	-9.7	A：Arg141、Asn219、Gly236、2[Glu275]、Gly281 B：Arg248	B: Tyr144、Arg287
	malonyl-ginsenoside Rc /11968724	-9.7	A：Glu132、Thr232、Gly236、2[Gly281] B：Lys143、Tyr144、His273、Arg287	—
	onjisaponin Z /134715185	-9.7	A：Arg141、Tyr237、Glu272、Glu275 B：Phe142、Lys143、His273、Asp282	A:Ala222、Val231
	memantine /4054	-6.2	B：Pro48	B: His13
PTGS2	polygalaxanthone III /11169063	-11.3	B：Asn34、2[His39]、Gly135、Pro154、Gln461	B: Cys47、Leu152、Pro153
	sibiricaxanthone A /21581292	-11.1	A：His39、Cys47、Ser49 B：Gln327	A: Cys47、Leu152、Pro153
	polygalaxanthone VIII /11261587	-10.9	A：Asn34、His39、Asp133、2[Gly135]、Gln461	A: Cys47、Leu152、Pro153
	arillanin A /11968790	-10.2	A：Asn34、Gly135	A: Val46、Pro153
	polygalasaponin XXI /10606178	-10.1	B：Asn34、2[Cys47]、Ser49、2[Asp157]	B: Tyr134

No competing interests reported.

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Screening of active ingredients in Kaixin Powder for Alzheimer’s disease based on molecular docking

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Abstract

Objective

Methods

Results

Conclusion

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1 Introduction

2 Results

2.1 Chemical Composition of Kaixin Powder

2.2 Targets of AD

2.3 Binding analysis of chemical constituents and targets

2.4 Interaction analysis for positive results.

3 Discussion

3.1 Chemical composition of Kaixin Powder and AD.

3.2 Clinical application and development progress of anti-AD drugs

3.3 Targets of AD

3.4 Results of molecular docking

4 Method

4.1 Collection and preparation of ligand molecules

4.2 Screening and preparation of receptor proteins.

4.3 Molecular docking

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References

Tables

Additional Declarations

Supplementary Files

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