Bioactive-Guided Phytochemical Investigations, In Vitro and In Silico Alpha-Glucosidase Inhibition of Two Vietnamese Medicinal Plants Dicranopteris linearis and Psychotria adenophylla.

Little is known about the chemical and biological profiles of Dicranopteris linearis and Psychotria adenophylla. No previous studies have investigated alpha-glucosidase inhibition using extracts from D. linearis and P. adenophylla. In this paper, bioactive-guided isolation procedures were applied to the plants D. linearis and P. adenophylla based on alpha-glucosidase inhibition. From the most active fractions, 20 compounds (DL1-DL13 and PA1-PA7) were isolated. The chemical structures were elucidated using spectroscopic data and compared with those available in the literature. These compounds were evaluated for alpha-glucosidase inhibition, while a molecular docking study was performed to elucidate the mechanisms involved. Consequently, D. linearis and P. adenophylla might serve as a good potential for developing new antidiabetic preparations.

The Pivotal Role of Neuropeptide Crosstalk from Ventromedial-PACAP to Dorsomedial-Galanin in the Appetite Regulation in the Mouse Hypothalamus.

We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) in the ventromedial hypothalamus (VMH) enhances feeding during the dark cycle and after fasting, and inhibits feeding during the light cycle. On the other hand, galanin is highly expressed in the hypothalamus and has been reported to be involved in feeding regulation. In this study, we investigated the involvement of the VMH-PACAP to the dorsomedial hypothalamus (DMH)-galanin signaling in the regulation of feeding. Galanin expression in the hypothalamus was significantly increased with fasting, but this increment was canceled in PACAP-knockout (KO) mice. Furthermore, overexpression of PACAP in the VMH increased the expression of galanin, while knockdown (KD) of PACAP in the VMH decreased the expression of galanin, indicating that the expression of galanin in the hypothalamus might be regulated by PACAP in the VMH. Therefore, we expressed the synaptophysin-EGFP fusion protein (SypEGFP) in PACAP neurons in the VMH and visualized the neural projection to the hypothalamic region where galanin was highly expressed. A strong synaptophysin-EGFP signal was observed in the DMH, indicating that PACAP-expressing cells of the VMH projected to the DMH. Furthermore, galanin immunostaining in the DMH showed that galanin expression was weak in PACAP-KO mice. When galanin in the DMH was knocked down, food intake during the dark cycle and after fasting was decreased, and food intake during the light cycle was increased, as in PACAP-KO mice. These results indicated that galanin in the DMH may regulate the feeding downstream of PACAP in the VMH.

Allium sativum@AgNPs and Phyllanthus urinaria@AgNPs: a comparative analysis for antibacterial application.

Although medicinal herbs contain many biologically active ingredients that can act as antibiotic agents, most of them are difficult to dissolve in lipids and absorb through biofilms in the gastrointestinal tract. Besides, silver nanoparticles (AgNPs) have been widely used as a potential antibacterial agent, however, to achieve a bactericidal effect, high concentrations are required. In this work, AgNPs were combined into plant-based antibiotic nanoemulsions using biocompatible alginate/carboxyl methylcellulose scaffolds. The silver nanoparticles were prepared by a green method with an aqueous extract of Allium sativum or Phyllanthus urinaria extract. The botanical antibiotic components in the alcoholic extract of these plants were encapsulated with emulsifier poloxamer 407 to reduce the particle size, and make the active ingredients both water-soluble and lipid-soluble. Field emission scanning electron microscopy (FESEM) and energy-dispersive X-ray (EDX) analysis showed that the prepared nanosystems were spherical with a size of about 20 nm. Fourier transform infrared spectroscopy (FTIR) confirmed the interaction of the extracts and the alginate/carboxyl methylcellulose carrier. In vitro drug release kinetics of allicin and phyllanthin from the nanosystems exhibited a retarded release under different biological pH conditions. The antimicrobial activity of the synthesized nanoformulations were tested against Escherichia coli. The results showed that the nanosystem based on Allium sativum possesses a significantly higher antimicrobial activity against the tested organisms. Therefore, the combination of AgNPs with active compounds from Allium sativum extract is a good candidate for in vivo infection treatment application.

In vitro antimycobacterial studies of flavonols from Bauhinia vahlii Wight and Arn.

Mycobacterial infections and fast-growing strains are increasing globally with 8 million new cases and 1.8 million fatalities per annum worldwide. The acid-fast bacterium, Mycobacterium tuberculosis (M.t), can spread diseases like tuberculosis (Tb) and weaken the immune system. In Ayurveda, the Bauhinia genus is most valued for the treatment of tuberculosis lymphadenitis. The objective of the present study is to identify anti-tubercular compounds from the under-investigated medicinal plant B. vahlii Wight and Arn. using bioassay guided isolation. The antimycobacterial activity was evaluated against non-virulent strains: Mycobacterium tuberculosis H37Ra (ATCC 25177) and Mycobacterium bovis BCG (ATCC 35743). Also, antibacterial and cytotoxicity activities were tested to identify the specificity of the isolated metabolites. Bioassay-guided isolation yielded three known flavonols, namely quercetin (1), ombuin (2), and kaempferol (3), from the methanolic extract of bark of B. vahlii. The results of antimycobacterial activity tests revealed that 2 showed much better mycobactericidal activity than 1 and 3 under ex vivo condition with minimum inhibitory concentration (MIC) values ranged from 0.05 ± 0.01 to 0.26 ± 0.01 nM, and half-maximal inhibitory concentration (IC50) values ranged from 2.85 ± 0.14 to 7.21 ± 1.09 nM against dormant and active forms, respectively. Also, compound 2 showed higher resistance with MIC values > 100 µg/mL against both Gram-positive and Gram-negative bacteria and the least cytotoxicity up to 100 µg/mL concentration against the tested series of cancer cell lines. The results revealed the Ayurvedic use of extracts of the Bauhinia genus for treating tuberculosis, and the key bioactive compounds were found to be flavonols (1-3). The present work provides the first evidence for the presence of antimycobacterial compounds in B. vahlii. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02672-4.

Subnudatones A and B, new trans-decalin polyketides from the cultured lichen mycobionts of Pseudopyrenula subnudata.

Chemical investigation of the cultured polyspore-derived mycobionts of a Pseudopyrenula subnudata lichen led to the isolation of two new compounds, subnudatones A and B (1 and 2), together with four known compounds, 1-(2-hydroxy-1,2,6-trimethyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl)ethanone (3), libertalide C (4), aspermytin A (5), and 6,7-dimethoxy-4-hydroxymellin (6). Their chemical structures were elucidated by extensive 1D and 2D NMR analysis and high resolution mass spectroscopy, and comparisons were made with the literature. The absolute configuration of 1 was defined unambiguously using single crystal X-ray crystallography. Compound 1 represents the first dimeric decalin polyketide to be found in nature. The in vitro cytotoxicity of 1 against two cancer cell lines (K562 and MCF-7) was evaluated. Compound 1 showed moderate cytotoxic activity with IC50 values of 23.5 ± 1.0 and 51.9 ± 1.4 µM, respectively.