Objectives Doxorubicin (DOX) is a commonly used chemotherapeutic drug. However, its non-target organ toxicities pose a serious problem. This study is to assess the protective role of Clerodendrum volubile leaf extract (CVE) against DOX-induced toxicities in rats. In addition, the inhibitory activities of three phytochemical compounds (Rutin, Gallic acid and Rosmarinic acid) from CVE against Carbonyl reductase 1 (CBR1) were examined. Methods Rats were randomly divided into 5 groups: (a) Control group rats were given 0.9% NaCl as vehicle, (b) DOX group: A single dose of DOX (25 mg/kg; i.p.) was administered and rats were sacrificed 4 days after DOX injection, while groups (c–e) CVE-treated DOX rat groups were given 125, 250 and 500 mg/kg body weight of extracts orally for 12 consecutive days; 8 days before, and 4 days after the DOX administration. Computational techniques were used to determine the inhibitory activities of the compounds against CBR1. Results DOX intoxication caused a significant increase (p<0.05) in serum marker enzymes: ALT, AST, ALP, LDH, CK activities. The levels of liver and heart tissues antioxidant parameters: GPx, SOD, CAT, and GSH were significantly (p<0.05) decreased in DOX-intoxicated rats with concomitant elevation of malondialdehyde levels. Pretreatment with CVE reversed the above trends. From the structural analysis, Rutin and RSA exhibited the highest binding free energies against CBR1, and also exhibited structural stability when bound with CBR1. Conclusions Our study indicates the protective effect of CVE when used in combination with doxorubicin thus improving its chemotherapeutic application via inhibition of CBR-mediated metabolism.

Oxidative stress occurs when the body’s enzymatic or non-enzymatic antioxidants are outweighed by endogenous or exogenous free radicals. Oxidative radicals, reactive oxygen species, and other biomolecule-damaging free radicals can be generated during normal cellular metabolism and react with proteins, lipids, and DNA. In the domains of biology and medicine, free radicals have become increasingly important. They can accumulate in a variety of ways, both endogenously and exogenously. Mitochondria are the primary source of cell-level endogenous reactive oxygen species. In several chronic and degenerative disorders, this results in tissue destruction. In addition to being produced endogenously, antioxidants can also be delivered exogenously to the biological system, most frequently through nutrition. Antioxidants are generally used to counteract the effects of free radicals produced by metabolic processes. In this chapter, the crucial function of reactive oxygen species in human health, as well as exploring the functioning of antioxidative defense systems in reducing toxicity caused by excess reactive oxygen species were discussed.

Background The prevalence of diarrhoea remains high despite efforts by governments and NGOs to reverse trend. This study investigated the antidiarrhoeal activity and mechanism of Spondias mombin leaf fraction rich in quercetin-3-O-β-D-glucopyranoside (Q3G-RF) because of the acclaimed therapeutic efficacy. Secretory, osmotic, and infectious diarrhoea models using castor oil, magnesium sulphate, and Shigella flexneri respectively were evaluated at the doses of 100, 200, and 400 mg/kg in Wistar rats. Enteropathy was induced with castor oil and magnesium sulphate, while gastrointestinal motility was determined with charcoal meal. Results Findings showed no mortality after 14 days of experimental period and no significant changes in behaviour, food, and water consumption. Relative to control, Q3G-RF inhibited the three models of diarrhoea, enteropathy, and gastrointestinal motility; bacterial colonies were reduced by Q3G-RF, while it improved the relative body weight of the animals. Q3G-RF also increased the intestinal concentration/activity of glucose, total protein, and Na+–K+ ATPase but reduced the concentration of TNF-α, PGE2, IL-1β, nitric oxide, Na+, K+, and Cl− in the diarrhoeal models. The intestinal fluid level of K+, Na+, and Cl− was significantly decreased by Q3G-RF in the enteropathy model. Length of the small intestine in the motility model was also increased by Q3G-RF, while peristaltic index and inhibition of peristalsis were reduced. Conclusion Overall, quercetin-3-O-β-D-glucopyranoside from Spondias mombin leaves demonstrated efficacy against infectious, secretory, and osmotic form of diarrhoeal and further justified its traditional use in the treatment of diarrhoea due to its antimotility, antisecretory, and antimicrobial properties by mechanism related to enhanced Na+–K+ ATPase, repressed nitric oxide, and suppressed prostaglandins.

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