Phenolic enriched fraction of Clerodendrum glandulosum Lindl. leaf extract ameliorates hyperglycemia and oxidative stress in streptozotocin-nicotinamide induced diabetic rats.

BACKGROUND: Clerodendrum glandulosum Lindl. is an important ethnomedicinal shrub of Northeast India, used by traditional healers to control various ailments like diabetes, hypertension, arthritis, etc. OBJECTIVES: The present study was conducted to explore the anti-hyperglycemic and antioxidative effects of the polyphenol-rich fraction (PRF) of C. glandulosum leaf extract and identification of its major bioactive compounds. Further, an in-silico molecular docking study was also performed to understand the molecular interactions of the identified major compounds with some target proteins associated with diabetic complications. MATERIALS AND METHODS: PRF was purified from the hydromethanolic (80% MeOH) extract of leaves and subjected to assessment of in-vitro antioxidant and anti-diabetic properties. It was also subjected to evaluate the ameliorative effect during streptozotocin-nicotinamide-induced hyperglycemia in Wistar albino rats. An in-silico molecular docking study was also performed to complement the in-vitro/in-vivo studies. RESULTS: Chemical analysis of PRF showed the presence of phenolics like caffeic acid, verbascoside, isoverbascoside, and apigenin, of which verbascoside (598.14 ± 1.24 mg/g) was found to be the principal compound. In-vitro studies showed potent antioxidant (IC50 of DPPH:32.45 ± 2.16 µg/mL; ABTS:39.08 ± 0.53 µg/mL) properties and excellent aldose reductase inhibition potential (IC50 2.18 ± 0.10 µg/mL). Treatment with PRF showed reduced blood glucose levels and increased plasma insulin levels. The results also indicate an improvement of endogenous antioxidants and suppression of inflammatory cytokines (IL-6 and TNF-α) comparable to the standard. Molecular docking studies predicted promising interactions between the identified molecules and the crucial amino acid residues of the enzymes involved in the development of hyperglycemia. CONCLUSION: This study revealed the antihyperglycemic and antioxidant potential of partially purified fraction PRF of C. glandulosum leaves.

Clerodendrum Glandulosum Lindl.: A Review of Ethnopharmacology, Pharmacological Potentials, and their Mechanism of Action.

Clerodendrum glandulosum Lindl. is popularly known for its traditional herbal remedies and therapeutic properties among the people of Northeast Indian communities, as well as Chinese traditional medicine. For the myriad pharmacological properties, viz., anti-hypertensive, hypolipidemic, hepatoprotective, anti-inflammatory, and neuroprotective, planting this species in kitchen gardens is a common practice to treat various ailments, especially hypertension, diabetes, and other metabolic complications. Different phytochemicals, representing the diverse classes of secondary metabolites comprising physiological and phytopharmaceutical significance, have been reported from C. glandulosum. Compounds with terpenoids, steroids, and phenolics are in demand in the pharmaceutical industry. An overview of the mechanism of action of the prominent compounds has also been collated for future research on C. glandulosum-based therapeutics. Current information focuses on this important medicinal plant's ethnomedicinal use, phytochemistry, pharmacology, associated mechanisms, and toxicology. This review will help explore this potential medicinal plant, which can pave the path for its application in the pharmaceutical industry.

Nutritional Composition and Pharmacological Activity of Musa balbisiana Colla Seed: An Insight into Phytochemical and Cellular Bioenergetic Profiling.

Musa balbisiana Colla belongs to the family Musaceae which is well-known for its nutritional and pharmacological properties. Here, we have analysed the phytochemical content and evaluated the nutritional, antioxidant, anti-glycation, α-amylase, and α-glucosidase inhibition potential. Moreover, for the first time, we have studied the bioenergetic profiles of the bioactive fractions of M. balbisiana seeds extract against oxidative stress-related mitochondrial and cellular dysfunction using XFe24 extracellular flux analyzer. M. balbisiana seeds have high nutritional values with significant levels of carbohydrates, starch, protein, and minerals (Ca, Na, Mg, Cu, Fe, and Zn). Bioactivity-guided fractionation of the methanolic extract of M. balbisiana seeds revealed that the ethyl acetate fraction (EAF) showed the highest antioxidant, anti-glycation, and phytochemical content as compared to other fractions. Moreover, the EAF showed a lower α-amylase inhibition and a higher α-glucosidase inhibitory activity. Most importantly, our GC-MS analyses of EAF revealed the presence of unique and previously unreported 14 phytochemical compounds. A strong correlation between the biological activities and total phenolic/tannin content was observed. In addition, the bioactive fraction of M. balbisiana seeds (EAF) improved the bioenergetic profiles of free fatty acid-induced oxidative stress with a concomitant increase in ATP production, and respiratory and glycolytic capacity. Altogether, our findings suggest that M. balbisiana seeds can be used as a natural supplement to boost antioxidant levels and combat oxidative stress and non-enzymatic glycation.

Ultrasound-Assisted Extraction of Verbascoside from Clerodendrum glandulosum Leaves for Analysis of Antioxidant and Antidiabetic Activities.

Verbascoside (VER) is a phenylethanoid glycoside compound found in Clerodendrum species and is an important part of traditional medicine. It is found in the leaves of Clerodendrum glandulosum, which is taken as a soup or vegetable and also utilized in traditional medicine by the people of Northeast India, especially against hypertension and diabetes. In the present study, VER was extracted from C. glandulosum leaves using ultrasound-assisted extraction through the solvent extraction method (ethanol-water, ethanol, and water). The ethanol extract had the highest phenolic and flavonoid contents, viz., 110.55 mg GAE/g and 87.60 mg QE/g, respectively. HPLC and LC-MS were used to identify the active phenolic compound, and VER was found to be the main component present in the extraction with a molecular weight of 624.59 g/mol. NMR (1H, 2D-COSY) analysis showed the presence of hydroxytyrosol, caffeic acid, glucose, and rhamnose in the VER backbone. Further, different antioxidant activities and antidiabetic and antihyperlipidemia enzyme markers' inhibition against VER-enriched ethanol extract were evaluated. The results showed that ultrasound extraction of polyphenols using ethanol from C. glandulosum could be a promising technique for the extraction of bioactive compounds.

Pharmacologically active chemical composite of Musa balbisiana ameliorates oxidative stress, mitochondrial cellular respiration, and thereby metabolic dysfunction.

The ripe fruit pulp of different Musa species is known for its excellent source of nutrient contents. Musa balbisiana (MB) is one such variety of Musa species, mainly found in the southern part of Asia, especially in the North-eastern part of India, remains unexplored despite its continuous use by the local traditional healers. The present study focuses on identifying and quantifying the active chemicals present in the ripe fruit pulp of Musa balbisiana (RFPMB) to understand its combined efficacy and nutritional benefit to control human metabolic complications specially related to diabetes and cardiovascular disorder. Characterization and confirmation through targeted LC-MS and HPLC-PDA based assays followed by quantitative analysis led us to identify the major bioactive compounds in RFPMB as shikimic acid, p-hydroxybenzoic acid, vanillic acid, ferulic acid, sinapic acid, caffeic acid, syringic acid, chlorogenic acid, trans-cinnamic acid, and two essential fatty acids; linolenic acid and linoleic acid. The ripe fruit pulp is further analyzed to understand the nutritional and mineral content and found a substantial presence of calcium and potassium (15.74 ± 0.43 and 395.20 ± 9.5 mg/100 g of raw pulp, respectively) compared to other reported varieties. The active portion of RFPMB reduces the production of ROS, the expression of inflammatory marker genes TNF-α and TGF-ß, and accelerates the mitochondrial oxygen consumption rate (OCR) by enhancing the basal respiration, maximal respiration, and ATP production capacity of the targeted cells. The present study concluded that, a particular phytopharmaceutical composition of RFPMB with 11-biomarker compounds might be an efficacious formulation for developing a value-added nutraceutical product in managing metabolic complications and its related oxidative stress. PRACTICAL APPLICATIONS: This study has provided the prior information regarding the potential nutraceutical and phytochemical advantages of Musa balbisiana (MB) fruit pulp over other reported banana varieties. The HPLC-based quantification will give a clear understanding of the food values in comparison of bioactive compounds present in the active fraction of RFPMB, which can be an effective phytopharmaceutical in combating metabolic disorders and oxidative stress. Overall this study will help to commercialize a value-added product from this variety of banana with proper scientific validation.