Peperomia pellucida L. is suspected to have gastro protector activity based on the results of previous research by Roslida and Aini (2009) which showed that Peperomia pellucida L. ethanol extract is able to provide a gastro protector effect with an effective dose of 100 mg/KgBW. The gastro protector activity of the messenger is produced by each metabolite compound with a different mechanism. Phytochemical screening of Peperomia pellucida L. showed that this plant contains secondary metabolites in the form of flavonoids, tannins, saponins, triterpenoids and steroids (Rachmawati and Rantelino, 2018). A previous study has found that dillapiole is the most active gastroprotective agent of Peperomia pellucida. However, the gastroprotective mechanism shown in dillapiole needs further study since the gastroprotective mechanism by dillapiole is not associated with endogenous nitric oxide or prostaglandins (Rojas-Martínez et al., 2013). Phytochemical test results extracted from Peperomia pellucida L. can be seen in Table 2.
Pachyrhizus erosus L. known to have gastroprotector activity based on research conducted by Pertiwi and Saputra (2019) where the administration of tuber juice Pachyrhizus erosus L. can reduce the number of ulcers that form and improve gastric histopathology due to ethanol exposure. Giving tuber juice Pachyrhizus erosus L.with a dose of 300 mg/kgBW gave a better gastroprotective effect than the juice of yam tubers combined with Raphanus sativus L.juice with the same dose (Pertiwi et al., 2021). Pachyrhizus erosus is known to contain flavonoids and saponins (Lukitaningsih, 2009). The isolation of Pachyrhizus erosus indicates the presence of the daidzein compounds; daidzein-7-O-β-glucopyranose, 5-hydroxy-daidzein-7-O-β-glucopyranose, and 8,9-furanyl-pterocarpan-3-. These compounds contain antioxidant activity and maybe one of the essential reasons for most of their biological properties, such as anti-diabetic, anticancer, immune modulation, and prevention of gastric ulcers reported from extract Pachyrhizus erosus (Jaiswal et al., 2021). Phytochemical test results extracted from Pachyrhizus erosus L. can be seen in Table 2.
Flavonoids have anti-ulcer and anti-inflammatory effects through several mechanisms of inhibition of K+ /H+ ATPase, decreased secretion of HCl, increased synthesis of PGE2 and COX-1 and inhibition of H. pylori growth, and antioxidants (Kalogeromitros et al. 2008). The mechanism of action of alkaloids as another gastroprotective is by accelerating wound healing and increasing gastric mucus production after injury due to inducing agents (Tan et al., 2002). Tannins are also known to have styptic properties, namely the ability to react with proteins in the gastric mucosal tissue layer. Its ability is useful to coat the outermost layer of the mucosa which makes it less permeable and more resistant to ulcers or irritation (Souza et al., 2012). Saponins provide gastroprotective activity through an increase in fibronectin, then the fibrin clot formed will be the basis for the reepithelialization process in the tissue. Therefore, if fibrin clots form quickly, fibroblasts will immediately proliferate to the wound area to immediately restore tissue (Indraswary, 2011).
Observations on the gastric anatomy of rats were carried out in each treatment group, the normal group did not show any ulcers, while the negative and positive control groups showed various characteristics of gastric ulcers such as hyperemia, hemorrhage petechiae, hemorrhage ecchymoses, hemorrhage purpura, or erosion (loss of gastric wall tissue). The ulcer index (IU) is calculated based on the comparison between the total score and the number of animals in each group. The mean total score of each group’s treatment was stated as an ulcer index or gastric ulcer index, which was then compared with the negative control group. The protective ability or protection ratio of the material towards the ulcer was calculated using the following formula by Saptarini and Suryasaputra (2011):
In the treatment group, the extract combination of Peperomia pellucida L. and Pachyrhizus erosus L. doses of 100 and 200 mg/kgBW showed hyperemia, hemorrhage petechiae, and hemorrhage ecchymoses, whereas at a dose of 400 mg/kgBW only hyperemia and hemorrhage petechiae were found. Anatomical images of the gastric of rat can be seen in Figure 2.
Observation of gastric ulcers was carried out by scoring each cross-section of the gastric using the Szabo method et al 1985 which has been modified. To avoid subjectivity to the results, the scoring is done by 3 observers. The results of observations of gastric ulcers in rats can be seen in Table 3. After obtaining the gastric ulcer index value, the value of the protection ratio was calculated. The results of the protection ratio can be seen in Table 4.
The histopathological observations of rats gastric were aimed to see the description of gastric tissue from damage by gastric ulcer-inducing compounds and to see the repair of gastric tissue after administration of a combination of extracts. Peperomia pellucida L. and Pachyrhizus erosus L.. The results of the histopathological picture of the gastric can be seen in Figure 3.
In the histopathological picture, the normal group showed a normal gastric histopathological picture and no abnormalities or changes in tissue structure were found. In the negative control group, there was a lot of tissue damage which was indicated by the disappearance of lesions on the mucosa, the presence of ulcers, bleeding, and hemorrhage, while in the positive control group, there was tissue damage with the presence of ulcers, bleeding, and lesions on the mucosa but only in some parts of the tissue. The treatment group were given extract Peperomia pellucida L. and Pachyrhizus erosus L. doses of 100, 200, and 400 mg/kgBW showed significant gastric improvement with increasing doses. This was shown in the combination of extract at a dose of 100 there were still ulcers and lesions, but at doses of 200 and 400 mg/kgBW there was an improvement in gastric cells and no more lesions on the mucosa were found.