Natural Compounds from Hatikana Extract Potentiate Antidiabetic Actions as Displayed by In Vivo Assays and Verified by Network Pharmacological Tools.

BACKGROUND: Hatikana is a traditional medicinal plant used to treat inflammation, urolithiasis, goiter, cancer, wounds and sores, gastrointestinal, tumor, tetanus, arthritis, hepatic damage, neurodegeneration, and other ailments. The goal of this study is to investigate the antidiabetic properties of Hatikana extract (HKEx) and to construct the effects of its natural constituents on the genes and biochemical indices that are connected with them. METHODS: HKEx was evaluated using GC-MS and undertaken for a three-week intervention in fructose-fed STZ-induced Wistar albino rats at the doses of HKEx50, HKEx100, and HKEx200 mg/kg bw. Following intervention, blood serum was examined for biochemical markers, and liver tissue was investigated for the mRNA expression of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD1) by RTPCR analysis. Most abundant compounds (oleanolic acid, 7α, 28-olean diol, and stigmasterol) from GC-MS were chosen for the network pharmacological assay to verify function-specific gene-compound interactions using STITCH, STRING, GSEA, and Cytoscape plugin cytoHubba. RESULTS: In vivo results showed a significant (P < 0.05) decrease of blood sugar, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine kinase (CK-MB), and lactate dehydrogenase (LDH) and increase of liver glycogen, glucose load, and serum insulin. Out of three antioxidative genes, catalase (CAT) and superoxide dismutase (SOD1) were found to be few fold increased. Oleanolic acid and stigmasterol were noticed to strongly interact with 27 target proteins. Oleanolic acid interacted with the proteins AKR1B10, CASP3, CASP8, CYP1A2, CYP1A2, HMGB1, NAMPT, NFE2L2, NQO1, PPARA, PTGIR, TOP1, TOP2A, UGT2B10, and UGT2B11 and stigmasterol with ABCA1, ABCG5, ABCG8, CTSE, HMGCR, IL10, CXCL8, NR1H2, NR1H3, SLCO1B1, SREBF2, and TNF. Protein-protein interaction (PPI) analysis revealed the involvement of 25 target proteins out of twenty seven. Cytoscape plugin cytoHubba identified TNF, CXCL8, CASP3, PPARA, SREBF2, and IL10 as top hub genes. Pathway analysis identified 31 KEGG metabolic, signaling, and immunogenic pathways associated with diabetes. Notable degree of PPI enrichment showed that SOD1 and CAT are responsible for controlling signaling networks and enriched pathways. CONCLUSION: The findings show that antioxidative genes have regulatory potential, allowing the HKEx to be employed as a possible antidiabetic source pending further validation.

Review of the Traditional Uses, Phytochemistry, and Pharmacological Activities of Rhoicissus Species (Vitaceae).

Species within the genus Rhoicissus (Vitaceae) are commonly used in South African traditional medicine. The current review discusses the occurrence, distribution, traditional uses, phytochemistry, and pharmacological properties of Rhoicissus species covering the period 1981-2020. The data reported were systematically collected, read, and analysed from scientific electronic databases including Scopus, Scifinder, Pubmed, and Google Scholar. Reported evidence indicates that species in this genus are used for the treatment of gastrointestinal complaints, sexually transmitted infections (STIs), and infertility, as well as to tone the uterus during pregnancy and to facilitate delivery. Pharmacological studies have further shown that members of the Rhoicissus genus display antidiabetic, uterotonic, ascaricidal, hepatoprotective, antioxidant, antimicrobial, anticancer, and anti-inflammatory properties. They are linked to the presence of bioactive compounds isolated from the genus. Hence, Rhoicissus species can potentially be an alternative therapeutic strategy to treat diseases and develop safer and more potent drugs to combat diseases. Plant species of this genus have valuable medicinal benefits due to their significant pharmacological potential. However, scientific investigation and information of the therapeutic potential of Rhoicissus remain limited as most of the species in the genus have not been fully exploited. Therefore, there is a need for further investigations to exploit the therapeutic potential of the genus Rhoicissus. Future studies should evaluate the phytochemical, pharmacological, and toxicological activities, as well as the mode of action, of Rhoicissus crude extracts and secondary compounds isolated from the species.

PLGA nanoparticles loaded with Gallic acid- a constituent of Leea indica against Acanthamoeba triangularis.

Acanthamoeba, a genus that contains at least 24 species of free-living protozoa, is ubiquitous in nature. Successful treatment of Acanthamoeba infections is always very difficult and not always effective. More effective drugs must be developed, and medicinal plants may have a pivotal part in the future of drug discovery. Our research focused on investigating the in vitro anti- acanthamoebic potential of Leea indica and its constituent gallic acid in different concentrations. Water and butanol fractions exhibited significant amoebicidal activity against trophozoites and cysts. Gallic acid (100 µg/mL) revealed 83% inhibition of trophozoites and 69% inhibition of cysts. The butanol fraction induced apoptosis in trophozoites, which was observed using tunnel assay. The cytotoxicity of the fractions and gallic acid was investigated against MRC-5 and no adverse effects were observed. Gallic acid was successfully loaded within poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles with 82.86% encapsulation efficiency, while gallic acid showed 98.24% in vitro release at 48 hours. Moreover, the gallic acid encapsulated in the PLGA nanoparticles exhibited 90% inhibition against trophozoites. In addition, gallic acid encapsulated nanoparticles showed reduced cytotoxicity towards MRC-5 compared to gallic acid, which evidenced that natural product nanoencapsulation in polymeric nanoparticles could play an important role in the delivery of natural products.

Transcriptome profiling reveals candidate flavonol-related genes of Tetrastigma hemsleyanum under cold stress.

BACKGROUND: Tetrastigma hemsleyanum Diels et Gilg is a valuable medicinal herb, whose main bioactive constituents are flavonoids. Chilling sensitivity is the dominant environmental factor limiting growth and development of the plants. But the mechanisms of cold sensitivity in this plant are still unclear. Also, not enough information on genes involved in flavonoid biosynthesis in T. hemsleyanum is available to understand the mechanisms of its physiological and pharmaceutical effects. RESULTS: The electrolyte leakage, POD activity, soluble protein, and MDA content showed a linear sustained increase under cold stress. The critical period of cold damage in T. hemsleyanum was from 12 h to 48 h. Expression profiles revealed 18,104 differentially expressed genes (DEGs) among these critical time points. Most of the cold regulated DEGs were early-response genes. A total of 114 unigenes were assigned to the flavonoid biosynthetic pathway. Fourteen genes most likely to encode flavonoid biosynthetic enzymes were identified. Flavonols of T. hemsleyanum might play a crucial role in combating cold stress. Genes encoding PAL, 4CL, CHS, ANR, FLS, and LAR were significantly up-regulated by cold stress, which could result in a significant increase in crucial flavonols (catechin, epicatechin, rutin, and quercetin) in T. hemsleyanum. CONCLUSIONS: Overall, our results show that the expression of genes related to flavonol biosynthesis as well as flavonol content increased in T. hemsleyanum under cold stress. These findings provide valuable information regarding the transcriptome changes in response to cold stress and give a clue for identifying candidate genes as promising targets that could be used for improving cold tolerance via molecular breeding. The study also provides candidate genes involved in flavonoid biosynthesis and may be useful for clarifying the biosynthetic pathway of flavonoids in T. hemsleyanum.

Structure characterization and adhesive ability of a polysaccharide from tendrils of Parthenocissus heterophylla.

In order to reveal the structure of the polysaccharide and its contribution to the biological adhesion system of Parthenocissus heterophylla, a water-soluble polysaccharide (PT-A) was isolated from tendrils using DEAE-cellulose and Sephadex G-100 columns. PT-A mainly consisted of a backbone of (1-->3)-linked-beta-D-Galp residues and substituted at 0-6 with side chains of (1-->5)-linked-alpha-L-Araf residues and glucomannopyranosyl residues. Individual polysaccharide chains of PT-A with the approximately height of 0.75 nm were observed by AFM. The analysis of force curves indicated that PT-A was a kind of elastic polysaccharide with a maximum adhesion force of 279.98 nN, which could be applied as a potential bio-adhesive.

Phytoalexins from the Vitaceae: biosynthesis, phytoalexin gene expression in transgenic plants, antifungal activity, and metabolism.

Resistance of plants to infection by phytopathogenic microorganisms is the result of multiple defense reactions comprising both constitutive and inducible barriers. In grapevine, the most frequently observed and best characterized defense mechanisms are the accumulation of phytoalexins and the synthesis of PR-proteins. Particular attention has been given here to stilbene phytoalexins produced by Vitaceae, specifically, their pathway of biosynthesis (including stilbene phytoalexin gene transfer experiments to other plants) and their biological activity together with fungal metabolism.