In recent years, indigenous medicinal plants exhibiting diverse biological activities have been explored in the amelioration of hepatotoxicity. This study investigates the protective effect of Monodora myristica (MM) on cadmium-induced liver damage in experimental animals. Male Wistar albino rats were maintained on 200 mg/L cadmium: Cd (Cd as CdCl2) in the animals’ main drinking water to induce hepatotoxicity. Added to this, the animals received aqueous extracts of MM at a dose of 200 or 400 and 20 mg/kg bw of Livolin forte (LF) for 21 days. At the end of the experiment, levels of serum enzyme biomarkers (alanine transaminase, alkaline phosphatase and aspartate transaminase) as well as total cholesterol (TC), triacylglyceride (TG) and malondialdehyde were significantly raised in the cadmium treated groups. Conversely, cadmium treatment elicited noticeable decrease in hepatic enzymatic and non-enzymatic antioxidants (reduced glutathione: GSH, catalase: CAT, superoxide dismutase: SOD). Co-treatment with MM at varying doses as well as LF considerably decreased the elevated levels of the serum biomarkers as well as TC, TG and malondialdehyde in the cadmium-treated groups in a dose dependant manner. Additionally, MM exhibited reversal potential on cadmium-toxicity at the tested doses as its administration was accompanied by a pronounced increase in GSH, SOD, and CAT levels. Histopathological results were parallel to these findings. These results demonstrates that aqueous extracts of MM is effective in the amelioration of hepatic damages arising from cadmium-induced toxicity, indicating that the antioxidant bio-constituents of MM play an important role in the prevention of liver toxicity possibly by inhibiting bioaccumulation of free radicals in animal models.

Currently, there is no known cure for diabetes. Different pharmaceutical therapies have been approved for the management of type 2 diabetes mellitus (T2DM), some are in clinical trials and they have been classified according to their route or mechanism of action. Insulin types, sulfonylureas, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, sodium–glucose cotransporter type 2 inhibitors, and incretin-dependent therapies (glucagon-like peptide-1 receptor agonists: GLP-1R, and dipeptidyl peptidase 4 inhibitors: DPP-4). Although some of the currently available drugs are effective in the management of T2DM, the side effects resulting from prolonged use of these drugs remain a serious challenge. GLP-1R agonists are currently the preferred medications to include when oral metformin alone is insufficient to manage T2DM. Medicinal plants now play prominent roles in the management of various diseases globally because they are readily available and affordable as well as having limited and transient side effects. Recently, studies have reported the ability of phytochemicals to activate glucagon-like peptide-1 receptor (GLP-1R), acting as an agonist just like the GLP-1R agonist with beneficial effects in the management of T2DM. Consequently, we propose that careful exploration of phytochemicals for the development of novel therapeutic candidates as GLP-1R agonists will be a welcome breakthrough in the management of T2DM and the co-morbidities associated with T2DM.

This study sought to investigate the possible protective role of Parkia biglobosa seed protein isolate (PBPi) against streptozotocin-induced hepatic damage and oxidative stress in diabetic male rats. Prior to animal experiments, a HPLC fingerprint of PBPi was recorded. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight). Diabetic rats were orally treated daily with PBPi (200 or 400 mg/kg body weight) or insulin (5 U/kg, i.p.) for 28 days. The degree of protection was evaluated using biochemical parameters such as malondialdehyde (MDA) levels, serum transaminases (ALT and AST), total protein, total glutathione (Total GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and interleukin-6 (IL-6) activities. Histology of liver sections was also performed. The HPLC fingerprint of PBPi revealed eleven distinct peaks; PBPi at tested doses significantly attenuates STZ-induced elevated levels of serum IL-6, ALT and AST; and hepatic TBARS levels. Hepatic antioxidants (Total GSH, GST, SOD, CAT) as well as total protein were markedly restored in a dose-dependent manner. Histopathological results strongly support the protective role of PBPi. These results suggest PBPi could confer protection by ameliorating hepatic damage and oxidative stress caused by STZ in animal model possibly via its anti-inflammatory and antioxidant properties.

Background: The increasing global incidence of breast cancer calls for the identification of new therapeutic targets and the assessment of possible neem-derived inhibitors by means of computational modeling and integrated genomic research. Methods: Originally looking at 59,424 genes throughout 42 samples, we investigated gene expression data from The Cancer Genome Atlas—Breast Cancer (TCGA-BRCA) dataset. We chose 286 genes for thorough investigation following strict screening for consistent expression. R’s limma package was used in differential expression analysis. The leading candidate’s protein modeling was done with Swiss-ADME and Discovery Studio. Molecular docking studies, including 132 neem compounds, were conducted utilizing AutoDock Vina. Results: Among the 286 examined, mitochondrially encoded cytochrome C oxidase III (MT—CO3) turned out to be the most greatly overexpressed gene, showing consistent elevation across all breast cancer samples. Protein modeling revealed a substantial hydrophobic pocket (volume: 627.3 ų) inside the structure of MT—CO3. Docking investigations showed five interesting neem-derived inhibitors: 7-benzoylnimbocinol, nimolicinol, melianodiol, isonimocinolide, and stigmasterol. Strong binding affinities ranging from −9.2 to −11.5 kcal/mol and diverse interactions with MT—CO3, mostly involving the residues Phe214, Arg221, and Trp58, these molecules displayed. With hydrophobic interactions dominant across all chemicals, fragment contribution analysis revealed that scaffold percentage greatly influences binding effectiveness. Stigmasterol revealed greater drug-likeness (QED = 0.79) despite minimal interaction variety, while 7-benzoylnimbocinol presented the best-balanced physicochemical profile. Conclusion: Connecting traditional medicine with current genomics and computational biology, this work proposes a methodology for structure-guided drug design and development using neem-derived chemicals and finds MT—CO3 as a potential therapeutic target for breast cancer.

This study seeks to investigate the possible protective role of the methanol extract of Piper guineense seeds against CCl₄-induced hepatotoxicity in an animal model. Hepatotoxicity was induced by administering oral doses of CCl₄ (1.2 g/kg bw) three times a week for three weeks. Group 1 (Control) and Group 2 (CCl₄) were left untreated; Piper guineense (PG; 400 mg/kg bw) was administered to Group 3 (T₁) by oral gavage for 14 days prior to the administration of CCl₄ and simultaneously with CCl₄; PG (400 mg/kg bw) was administered simultaneously with CCl₄ in Group 4 (T₂); and Livolin forte (20 mg/kg bw) was administered simultaneously with CCl₄ in Group 5 (T₃), the standard drug group. The administration of CCl₄ induces histopathological alteration in the liver, with concomitant increased activities of serum hepatic marker enzymes associated with increased levels of lipid peroxidation. Similarly, there was decrease in non-enzymatic (reduced glutathione) and enzymatic antioxidants (glutathione S-transferase), superoxide dismutase, and catalase. An elevation in serum triglyceride and total cholesterol levels was noticed along with decreased levels of serum total protein. Treatment with PG 400 mg/kg bw exhibited excellent modulatory activity with respect to the different parameters studied by reversing all the above-mentioned biochemical changes significantly in the experimental animals. These results suggest that PG offered protection comparable to that of Livolin forte with better efficacy when pre-treated with 400 mg/kg bw 14 days prior to CCl₄-exposure.

Type 2 diabetes remains one of the leading causes of death worldwide. Persistent hyperglycemia within a diabetic state is implicated in the generation of oxidative stress and aggravated inflammation that is responsible for accelerated modification of pancreatic beta cell structure. Here we investigated whether a lanosteryl triterpene, methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA-3), isolated from Protorhus longifolia can improve glucose tolerance and pancreatic beta cell ultrastructure by reducing oxidative stress and inflammation in high fat diet and streptozotocin-induced type 2 diabetes in rats. In addition to impaired glucose tolerance, the untreated diabetic rats showed increased fasting plasma glucose and C-peptide levels. These untreated diabetic rats further demonstrated raised cholesterol, interleukin-6 (IL-6), and lipid peroxidation levels as well as a destroyed beta cell ultrastructure. Treatment with RA-3 was as effective as metformin in improving glucose tolerance and antioxidant effect in the diabetic rats. Interestingly, RA-3 displayed a slightly more enhanced effect than metformin in reducing elevated IL-6 levels and in improving beta cell ultrastructure. Although the involved molecular mechanisms remain to be established, RA-3 demonstrates a strong potential to improve pancreatic beta cell ultrastructure by attenuating impaired glucose tolerance, reducing oxidative stress and inflammation.