Flavonoid from Moringa oleifera leaves revisited: A review article on in vitro, in vivo, and in silico studies of antidiabetic insulin-resistant activity.

Diabetes mellitus (DM) occurs when the body experiences insulin deficiency or is unable to use insulin appropriately, which increases the blood glucose levels over the threshold. Moringa oleifera leaf is a widely used and scientifically proven herbal medicine to treat DM. The demand for the development of new drugs has prompted in vitro, in vivo, and in silico studies of antidiabetic insulin-resistant activity. This study aims to conduct a comprehensive study of the types of flavonoid and nonflavonoid compounds that have antidiabetic activity in insulin resistance mellitus using in vitro, in vivo, and in silico approaches. The literature review was conducted in accordance with the offered reporting items for systematic review. Major bibliographic databases, i.e. Scopus, PubMed, and DOAJ, covering original articles about the aforementioned issues between January 1, 2011 and December 31, 2021 were used. In this study, 274 articles were retrieved, of which 4 were duplicates, and after the titles were read, only 108 were left for analysis. After the abstract screening, 32 articles were eligible for the literature review. The results exhibit that flavonoids, including quercetin and kaempferol, and nonflavonoids, including anthraquinone, cytogluside (glycoside), hemlock tannin, phenolic steroid, and 2-phenylchromenylium (anthocyanins), have potential insulin-resistant antidiabetic activity in vitro, in vivo, and in silico. This has broadened the research into the development of new drugs.

Application of Response Surface Methodology (RSM) for the Optimization of Ultrasound-Assisted Extraction (UAE) of Moringa oleifera: Extraction Yield, Content of Bioactive Compounds, and Biological Effects In Vitro.

This study optimized ultrasound-assisted extraction conditions to maximize the extraction yield, total flavonoid content (TFC), total phenolic content (TPC), and DPP IV enzyme inhibitory activity from Moringa oleifera. The four UAE factors, solvent ratio (A), solvent-solid ratio (B), extraction temperature (C), and extraction time (D), were optimized using response surface methodology (RSM). A Box-Behnken design was used for the experimental design. The optimal conditions were found to be a 50% v/v solvent ratio, a 30% v/w solvent-solid ratio, 35 °C extraction temperature, and 45 min extraction time. The experimental value of extraction yield (R1), TFC (R2), TPC (R3), and DPP IV enzyme inhibitory activity (R4) (87.99% w/w, 56.63 mg QE/g extract, 97.26 mg GAE/g extract, and 93.32% inhibition, respectively) agreed with those predicted by RSM models (88.10% w/w, 56.61 mg QE/g extract, 97.16 mg GAE/g extract, and93.38% inhibition, respectively), thus demonstrating the appropriateness of the model used and the ability of the RSM to optimize the extraction conditions. Excellent DPP IV enzyme inhibitory activity was exhibited by M. oleifera compared with the standard, sitagliptin. While the modeled equation fits the data, the t-test is not significant, suggesting that the experimental values agree with those predicted by the RSM-BBD.

Potential SARS-CoV-2 3CLpro inhibitors from chromene, flavonoid and hydroxamic acid compound based on FRET assay, docking and pharmacophore studies.

This present study reports some natural products and one hydroxamic acid synthetic compound which were previously reported as matrix metalloproteinase-9 (MMP-9) inhibitors to be evaluated for their inhibition toward severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) 3-chymotrypsin-like protease (3CLpro). This enzyme is one of the proteins responsible for this coronaviral replication. Two herbal methanolic extracts i.e., Averrhoa carambola leaves and Ageratum conyzoides aerial part demonstrate >50% inhibition at 1000 µg/mL. Interestingly, apigenin, one of flavonoids, demonstrates 92% inhibition at 250 µg/mL (925 µM) as well as hydroxamic acid compound, N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid (NNGH), which shows 69% inhibition at 100 µM. The in vitro results are supported by the docking studies revealing that the binding mode of both compounds is mainly by interacting with GLU166 residue in the hydrophobic pocket of the 3CLpro. Pharmacophore mapping further supported the results by confirming that the in vitro activities of both compounds are due to their pharmacophore features employing hydrogen bond acceptor (HBA), hydrogen bond donor (HBD) and hydrophobic. Gas Chromatography-Mass Spectrometry (GC-MS) analysis reported chromene compounds in Ageratum conyzoides aerial part methanolic extract are potential to be this enzyme inhibitor candidate. These all results reflect their potencies to be SARS-CoV-2 inhibitors through 3CLpro inhibition mechanism.

Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study (Part II).

In our previous work, the partitions (1 mg/mL) of Ageratum conyzoides (AC) aerial parts and Ixora coccinea (IC) leaves showed inhibitions of 94% and 96%, respectively, whereas their fractions showed IC50 43 and 116 µg/mL, respectively, toward Matrix Metalloproteinase9 (MMP9), an enzyme that catalyzes a proteolysis of extracellular matrix. In this present study, we performed IC50 determinations for AC n-hexane, IC n-hexane, and IC ethylacetate partitions, followed by the cytotoxicity study of individual partitions against MDA-MB-231, 4T1, T47D, MCF7, and Vero cell lines. Successive fractionations from AC n-hexane and IC ethylacetate partitions led to the isolation of two compounds, oxytetracycline (OTC) and dioctyl phthalate (DOP). The result showed that AC n-hexane, IC n-hexane, and IC ethylacetate partitions inhibit MMP9 with their respective IC50 as follows: 246.1 µg/mL, 5.66 µg/mL, and 2.75 × 10-2 µg/mL. Toward MDA-MB-231, 4T1, T47D, and MCF7, AC n-hexane demonstrated IC50 2.05, 265, 109.70, and 2.11 µg/mL, respectively, whereas IC ethylacetate showed IC50 1.92, 57.5, 371.5, and 2.01 µg/mL, respectively. The inhibitions toward MMP9 by OTC were indicated by its IC50 18.69 µM, whereas DOP was inactive. A molecular docking study suggested that OTC prefers to bind to PEX9 rather than its catalytic domain. Against 4T1, OTC showed inhibition with IC50 414.20 µM. In conclusion, this study furtherly supports the previous finding that AC and IC are two herbals with potential to be developed as triple-negative anti-breast cancer agents.