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The considerably high incidence of cardiovascular disease in Indonesia has attracted scientists to investigate various plant and fruit extracts as preventive agents. Averrhoa bilimbi (AB) is rich in bioactive constituents that may be effective in preventing indicators of hypertension. This study evaluated the roles of AB extract in increasing serum nitric oxide (NO) concentration and vascular dilatation in ethanol-induced hypertensive rats. A total of 24 male Wistar rats (Rattus norvegicus) were divided equally into 4 treatment groups (n=6): P0 (control group, administered placebo); P1 [administered captopril 3 mg/kg body weight (BW) orally]; P2 (administered AB extract at 20 g/kg BW); and P3 (administered AB extract at 40 g/kg BW). The AB extract was obtained from fresh AB macerated in 96% ethanol and was subjected to bioactive compounds identification using thin layer chromatography. After pretreatment with ethanol for 15 days, treatments were administered daily for 14 days. All rats were measured for tail blood pressure by the tail-cuff method and NO concentrations by avidin-horseradish peroxidase sandwich-enzyme-linked immunosorbent assays. All rats were sacrificed to collect blood vessels for histopathology. The results showed that AB extracts contained flavonoids, saponins, polyphenols, essential oils, and anthraquinone. Treatment with AB extract at a dose of 40 mg/kg BW significantly increased NO concentrations (P<0.05). Histopathological analysis showed that AB extracts inhibited endothelial pyknosis, intimal body, and adventitial leukocyte infiltration of posterior vena cava blood vessels. These results suggest that the protective effect of AB extracts is associated with NO concentration in the blood by inhibiting blood vessel dysfunction.

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The aims of this study is to evaluate molecular docking of flavonoid Coleus amboinicus (CA) extracts in transforming growth factor-1b and lowering MDA concentration on cisplatin-induced in Wistar rat. Eighteen male Wistar rats (Rattus norvegicus), 3 months of age with a body weight (BW) of 150-200 g, were allocated into three groups, with six animals per group. The control group received aquadest (P0), the treatment group were treated with single doses of cisplatin (5 mg/kg bw., ip) (P1) and  received 100 mg/kg bw of the CA extracts (P2) respectively for 7 days. Bloods collected for analysis of serum alkaline phospatase (AP), Blood Nitrogen Urea (BUN) and Malondialdehid (MDA) concentrations. The levels of Malondialdehid (MDA) concentrations were analysed by Avidin-Horseradish Peroxidase (HRP) Sandwich-ELISA. All groups were sacrified for histopathology. Coleus amboinicus extract significantly decreased the level of AP, BUN and MDA concentrations compared to the control group (p<0.05). The level of MDA could be detected by its level significantly decreased in CA treatment group (p<0.05). Coleus amboinicus (CA) extract has a flavonoid as a marker compound of CA extract has stronger bind to the TGF-β1receptor than its of 3WA_601 ligand in silico analyzed. In histopathological examination showed that cisplatin-induced could alter severe multifocal hemorrhage, interstitial congestion, cell inflammatory, acute glomerular and tubular injury with necrotic cells. Immunohistochemical staining labeled with TGF-1β monoclonal antibodies (Mab) showed marked expression of brownish color aggregates on the surface of tubular epithelial cells and around glomerular mesangial cells in the CA treatment group. This study was concluded that CA extract is inhibited renal tissue injuries by lowering MDA and increasing TGF-1b expression on cisplatin-induced rats. Flavonoid as marker of CA extract has stronger bind to TGF-1b receptor by in silico.

Background and Aim: Coleus amboinicus (CA) plants are known to exert antibacterial and anti-inflammatory effects and demonstrate antiproliferative effects against cancer cells. This study aimed to investigate the activity of CA extract on the expression of transforming growth factor-1β (TGF-1β) in cisplatin-induced nephropathy in Wistar rats (Rattus norvegicus). Materials and Methods: CA was obtained from fresh leaves of CA and was extracted using 96% ethanol maceration. This blinded, controlled, randomized post-test study assigned 24 Wistar rats to three groups (n=8). Negative controls received normal saline (P0), nephropathy was induced in rats by cisplatin (5 mg/kg, IP) (P1), and treated with ethanolic coleus extract (500 mg/kg, PO) (P2), respectively, for 7 days. Nephropathy was induced on the 4th day. All rats were sacrificed on the 8th day for blood and kidney sample collection. Concentrations of blood urea nitrogen (BUN), creatinine, and alkaline phosphatase were analyzed using colorimetric analysis. A semi-quantitative analysis was performed on sectioned kidneys to determine the numbers of positive cells for TGF-1β expression and to evaluate structural and functional alterations in the kidneys using histopathological and immunohistochemical staining. Results: The concentrations of BUN, creatinine, and alkaline phosphatase from blood samples in the treatment group were significantly lower than those of the control group (p<0.05). Morphological evaluation of the tubular interstitium and glomeruli revealed that necrotic, degenerating, and infiltration of cells significantly decreased in the treatment group compared to the control group (p<0.05). The mean immunostaining scores indicating the presence of TGF-1β were 7.8 in the ethanolic coleus extract group, 3 in the induction group, and 2.3 in the control group. The expression scores for TGF-β1 were significantly different between the ethanolic coleus extract treatment and control group (p<0.05). Conclusion: Our results suggest that in Wistar rats with cisplatin-induced nephropathy, CA extract inhibits pathological lesions by regulating the renal expression of TGF-1β in areas containing the renal tubules and glomeruli. Keywords: cisplatin, Coleus amboinicus, nephropathy, transforming growth factor-1β.