Anticarcinogenic activity of methanol extract of Melastoma malabathricum leaves is attributed to the presence of phenolics compounds and the activation of endogenous antioxidant system

Melastoma malabathricum (M. malabathricum) extracts have been reported to exert various pharmacological activities including antioxidants, anti-inflammatory and antiproliferative activities. The objective of the present study was to determine the anticarcinogenic activity of its methanol extract (MEMM) against the azoxymethane (AOM)-induced early colon carcinogenesis in rats. Rats were randomly assigned to five groups (n=6) namely normal control, negative control, and treatment (50, 250 or 500 mg/kg of MEMM) groups. Colon tissues were harvested for histopathological analysis and endogenous antioxidant system determination. MEMM was also subjected to HPLC analysis. Findings showed that MEMM significantly (p<0.05) reversed the AOM-induced carcinogenicity by: i) reducing the formation of aberrant crypt foci (ACF) in colon tissues, and; ii) enhancing the endogenous antioxidant activity (catalase, superoxide dismutase and glutathione peroxidase). Moreover, various phenolics has been identified in MEMM. In conclusion, MEMM exerts the in vivo anticarcinogenic activity via the activation of endogenous antioxidant system and synergistic action of phenolics.

Hypericum spp.—An Overview of the Extraction Methods and Analysis of Compounds

The Hypericum genus contains one of the few genera of flowering plants that contains a species with authorization for marketing as a traditional medicine, H. perforatum. Due to the fact that this is a large genus, comprising numerous species, a large amount of interest has been shown over the years in the study of its various pharmacological activities. The chemical composition of these species is quite similar, containing compounds belonging to the class of phloroglucinol derivatives, naphthodianthrones, phenols, flavonoids and essential oils. Taking all of this into consideration, the present study aims to offer an overview of the species of the genus from the point of view of their extraction techniques and analysis methods. An extensive study on the scientific literature was performed, and it revealed a wide range of solvents and extraction methods, among which ethanol and methanol, together with maceration and ultrasonication, are the most frequent. Regarding analysis methods, separation and spectral techniques are the most employed. Therefore, the present study provides necessary data for future studies on the species of the genus, offering a complete overview and a possible basis for their development.

Effects on mammalian cell transcriptome reveal a plant extract's medicinal properties: Potential anti-COVID-19 and anti-cancer properties of Sarcopoterium spinosum

Plants with medicinal properties are usually identified based on traditional medicine knowledge or using low-throughput screens for specific pharmacological activities. Here, we suggest a different approach to uncover a range of pharmacological activities of a chosen plant extract without the need for functional screening. This tactic predicts biological activities of a plant extract based on pathway analysis of transcriptome changes caused by the extract in mammalian cell culture. In this work, we identified transcriptome changes after exposure of cultured cells to an extract of the medicinal plant Sarcopoterium spinosum. Gene Set Enrichment Analysis (GSEA) confirmed known anti-inflammatory and anti-cancer activities of the extract and predicted novel biological effects on oxidative phosphorylation and interferon pathways. Experimental validation of these pathways uncovered strong activation of autophagy, including mitophagy, and astounding protection from SARS-CoV-2 infection. Our study shows that gene expression analysis alone is insufficient for predicting biological effects since some of the changes reflect compensatory effects, and additional biochemical tests provide necessary corrections. In conclusion, this study defines the advantages and limitations of an approach towards predicting the biological and medicinal effects of plant extracts based on transcriptome changes caused by these extracts in mammalian cells.

Paeonol Ameliorates Chronic Itch and Spinal Astrocytic Activation via CXCR3 in an Experimental Dry Skin Model in Mice

Paeonol is a bioactive phenol presents mainly in Paeonia suffruticosa Andr. (Paeoniaceae), Paeonia lactiflora Pall., and Dioscorea japonica Thunb. (Dioscoreaceae), harboring various pharmacological activities including anti-inflammatory, antioxidant, immune regulatory activity and reverse chemoresistance. Recent reports revealed paeonol exhibited good effects on chronic dermatitis, such as atopic dermatitis (AD) and psoriasis. However, whether paeonol is effective for dry skin disease and its mechanism of action still remain unclear. In this study, we analysed the effects of paeonol on a mouse model of dry skin treated with acetone-ether-water (AEW), which showed impressive activities in reducing scratching behavior and skin inflammation. To elucidate the underlying molecular targets for the anti-pruritic ability of paeonol, we screened the expression of possible chemokine pathways in the spinal cord. The expression of CXCR3 was significantly alleviated by paeonol, which increased greatly in the spinal neurons of AEW mice. In addition, treatment of paeonol significantly inhibited AEW-induced expression of astrocyte activity-dependent genes including Tlr4, Lcn2 and Hspb1 et al. The inhibitory effects of paeonol on scratching behavior and astrocytic activation in the spinal cord induced by AEW were abolished when CXCR3 was antagonized or genetically ablated. Taken together, our results indicated that paeonol can ameliorate AEW-induced inflammatory response and itching behavior, and reduce the expression of spinal astrocyte activity-dependent genes induced by AEW, which are driven by CXCR3.

Nanomedicine Based on Natural Products: Improving Clinical Application Potential

Natural products have antitumor, anti-inflammatory, antioxidant, and other pharmacological activities and are an important source of drugs for prevention and treatment of various diseases. However, the inherent defects of natural products in physiological media such as poor solubility and stability and short biological half-life limit their clinical application. In recent years, more and more attention has been paid to the science of drug delivery by nanoscale materials. A large number of in vitro and in vivo studies have further confirmed the efficacy and safety of nanomedicine based on natural products in preclinical models of various diseases. In this review, we summarized the achievements of nanomaterials in improving the efficacy of natural products, introduced the research progress in several key fields of natural product-based nanomedicine in medical application, and discussed the challenges and prospects of clinical transformation of nanomedicine.

Ethnomedicinal uses, phytochemistry, pharmacology, and toxicity of the genus Nymphaea L.: A review.

Background: Plants from the genus Nymphaea L. have been used for decades to treat various diseases, including dysentery, diarrhea, uterine cancer, gonorrhea, inflammation conditions, among others. The present study aims to critically analyze comprehensive literature on ethnopharmacological uses, phytochemistry, pharmacology, and toxicity of Nymphaea L. Methods: The available information on Nymphaea L. was obtained from textbooks, theses, as well as published articles through libraries, and electronic databases. Results: More than 150 compounds, including flavonoids, phenolics, alkaloids, miscellaneous compounds, etc. were identified from Nymphaea L. extracts and pure molecules from Nymphaea L. exhibited a wide range of pharmacological activities, including antimicrobial, anti-inflammatory, anticancer, immunomodulatory, hepatoprotective, antioxidant, cytotoxic, among others. Conclusion: Referring to in vitro and in vivo studies, Nymphaea sp. are very promising medicinal plants, however, more in vivo experiments, cytotoxicity tests, and detailed mechanisms of action of their extracts, and compounds are recommended to confirm their ethnomedicinal claims into scientific rationale-based information.

SCM-198 Prevents Endometriosis By Reversing Low Autophagy Levels Of Endometriotic Stromal Cells Via Inhibiting TNF-Α-Aromatase-Estrogen-Erα Pathway And Promoting PR Expression

Background: Endometriosis (EMS), an estrogen-dependent disease, is characterized by dysregulated inflammation and increased estrogen in ectopic lesions. However, the crosstalk and pathogenic mechanism of inflammation and estrogen has not been fully explored. SCM-198 is the synthetic form of leonurine with multiple pharmacological activities. Whether SCM-198 could inhibit the progress of EMS by regulating inflammation and estrogen signaling remains unknown. Methods: The therapeutic effects and potential mechanisms of SCM-198 on EMS were analyzed by establishing EMS mice models and performing RNA-seq assay. ELISA was performed to detect estrogen and TNF-α concentration in normal endometrial stromal cells (nESCs) and ectopic endometrial stromal cells (eESCs), with or without SCM-198 treatment. Western blotting, RNA silencing and plasmid overexpression were utilized to analyze the relationship among inflammation, endocrine and autophagy as well as the regulation of SCM-198 on inflammation-endocrine-autophagy axis. Results: Increased estrogen-ERα signaling and decreased PR expression co-led to the hypo-autophagy state in eESCs, which further inhibited the apoptosis of eESCs. Highly expressed TNF-α in eESCs enhanced low-autophagy mediated anti-apoptosis effect by activating aromatase-estrogen-ERα signaling. SCM-198 inhibited the growth of ectopic lesions in EMS mouse model and promoted the apoptosis of eESCs both in vivo and in vitro. The apoptosis effect of SCM-198 on eESCs were realized by upregulating the autophagy level via inhibiting TNF-α activated aromatase-estrogen-ERα signaling and increasing PR expression. Conclusion: Inflammation facilitated the progress of EMS by disturbing estrogen regulatory axis. SCM-198 restrained the growth of EMS by regulating inflammation-endocrine-autophagy axis.

Pyrazole Containing Anti-HIV Agents: An Update

Background: Pyrazole scaffolds have gained importance in drug discovery and development for various pharmacological activities like antiviral, antifungal, anticancer, antidepressant, anti-inflammatory, antibacterial, etc. Additionally, the pyrazole moiety has shown potent anti-HIV activity as a core heterocycle or substituted heterocycles derivatives (mono, di, tri, tetra, and fused pyrazole derivatives). To assist the development of further potential anti-HIV agents containing pyrazole nucleus, here we have summarized pyrazole containing anti-HIV compounds that have been reported by researchers all over the world for the last two decades. Objective: The present review concentrates on an assortment of pyrazole containing compounds, particularly for potential therapeutic activity against HIV. Methods: Google Scholar, Pubmed, and SciFinder were searched databases with ‘‘pyrazol’’ keywords. Further, the year of publication and keywords ‘‘Anti-HIV’’ filter was applied to obtain relevant reported literature for anti-HIV agents containing pyrazole as a core or substituted derivatives. Results: This review article has shown the comprehensive compilation of 220 compounds containing pyrazole nucleus and possessing anti-HIV activity by sorting approximately 40 research articles from 2001 to date. 1-(4-Benzoylpiperazin-1-yl)-2-(4-fluoro-7-(1H-pyrazol-3-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (13), 3-(3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4-fluoro-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxamide (31), 3-(3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4-fluoro-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxamide (88), 3-cyanophenoxypyrazole derivative (130), and 4-(4-chlorophenyl)-5-(4-methyl-5-((4-nitrophenyl)diazenyl)thiazol-2-yl)-3-phenyl-5,6-dihydro-4H-pyrazolo[4,3-d]isoxazole (178) were the most potent mono-, di-, tri-, tetra-substituted, and fused pyrazole derivatives, respectively, which have shown potent anti-HIV activity among all the described derivatives as compared with standard anti-HIV drugs. Conclusion: This review article provides an overview of the potential therapeutic activity of pyrazole derivatives against HIV that will be helpful for designing pyrazole containing compounds for anti-HIV activity.

Evaluation of Substituted Pyrazole-Based Kinase Inhibitors in One Decade (2011–2020): Current Status and Future Prospects

Pyrazole has been recognized as a pharmacologically important privileged scaffold whose derivatives produce almost all types of pharmacological activities and have attracted much attention in the last decades. Of the various pyrazole derivatives reported as potential therapeutic agents, this article focuses on pyrazole-based kinase inhibitors. Pyrazole-possessing kinase inhibitors play a crucial role in various disease areas, especially in many cancer types such as lymphoma, breast cancer, melanoma, cervical cancer, and others in addition to inflammation and neurodegenerative disorders. In this article, we reviewed the structural and biological characteristics of the pyrazole derivatives recently reported as kinase inhibitors and classified them according to their target kinases in a chronological order. We reviewed the reports including pyrazole derivatives as kinase inhibitors published during the past decade (2011–2020).