Polygonumins A, a newly isolated compound from the stem of Polygonum minus Huds with potential medicinal activities

Polygonumins A, a new compound, was isolated from the stem of Polygonum minus. Based on NMR results, the compound’s structure is identical to that of vanicoside A, comprising four phenylpropanoid ester units and a sucrose unit. The structure diferences were located at C-3″″′. The cytotoxic activity of polygonumins A was evaluated on several cancer cell lines by a cell viability assay using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The compound showed the highest antiproliferative (p<0.05) activities against K562 (Human Leukaemia Cell Line), MCF7 (Human breast adenocarcinoma cell line), and HCT116 (Colorectal cancer cells) cells. Cytotoxic studies against V79–4 cells were carried out and showed that polygonumins A was toxic at 50µg/ml, suggesting that this compound may be used as an anticancer drug without afecting normal cells. Polygonumins A also showed promising activity as an HIV-1 protease inhibitor with 56% relative inhibition. Molecular docking results indicated that the compound possesses high binding afnity towards the HIV protease over the low binding free energy range of -10.5 to -11.3kcal/mol. P. minus is used in Malaysian traditional medicine for the treatment of tumour cells. This is the frst report on the use of P. minus as an HIV-1 protease inhibitor

<i>Cleistocalyx nervosum</i> var. <i>paniala</i> Berry Seed Protects against TNF-α-Stimulated Neuroinflammation by Inducing HO-1 and Suppressing NF-κB Mechanism in BV-2 Microglial Cells

Sustained inflammatory responses have been implicated in various neurodegenerative diseases (NDDs). Cleistocalyx nervosum var. paniala (CN), an indigenous berry, has been reported to exhibit several health-beneficial properties. However, investigation of CN seeds is still limited. The objective of this study was to evaluate the protective effects of ethanolic seed extract (CNSE) and mechanisms in BV-2 mouse microglial cells using an inflammatory stimulus, TNF-α. Using LC-MS, ferulic acid, aurentiacin, brassitin, ellagic acid, and alpinetin were found in CNSE. Firstly, we examined molecular docking to elucidate its bioactive components on inflammation-related mechanisms. The results revealed that alpinetin, aurentiacin, and ellagic acid inhibited the NF-κB activation and iNOS function, while alpinetin and aurentiacin only suppressed the COX-2 function. Our cell-based investigation exhibited that cells pretreated with CNSE (5, 10, and 25 μg/mL) reduced the number of spindle cells, which was highly observed in TNF-α treatment (10 ng/mL). CNSE also obstructed TNF-α, IL-1β, and IL-6 mRNA levels and repressed the TNF-α and IL-6 releases in a culture medium of BV-2 cells. Remarkably, CNSE decreased the phosphorylated forms of ERK, p38MAPK, p65, and IκB-α related to the inhibition of NF-κB binding activity. CNSE obviously induced HO-1 protein expression. Our findings suggest that CNSE offers good potential for preventing inflammatory-related NDDs

Thunbergia laurifolia Leaf Extract Inhibits Glutamate-Induced Neurotoxicity and Cell Death through Mitophagy Signaling

Oxidative stress plays a crucial role in neurodegeneration. Therefore, reducing oxidative stress in the brain is an important strategy to prevent neurodegenerative disorders. Thunbergia laurifolia (Rang-jued) is well known as an herbal tea in Thailand. Here, we aimed to determine the protective effects of T. laurifolia leaf extract (TLE) on glutamate-induced oxidative stress toxicity and mitophagy-mediated cell death in mouse hippocampal cells (HT-22). Our results reveal that TLE possesses a high level of bioactive antioxidants by LC–MS technique. We found that the pre-treatment of cells with TLE prevented glutamate-induced neuronal death in a concentration-dependent manner. TLE reduced the intracellular ROS and maintained the mitochondrial membrane potential caused by glutamate. Moreover, TLE upregulated the gene expression of antioxidant enzymes (SOD1, SOD2, CAT, and GPx). Interestingly, glutamate also induced the activation of the mitophagy process. However, TLE could reverse this activity by inhibiting autophagic protein (LC3B-II/LC3B-I) activation and increasing a specific mitochondrial protein (TOM20). Our results suggest that excessive glutamate can cause neuronal death through mitophagy-mediated cell death signaling in HT-22 cells. Our findings indicate that TLE protects cells from neuronal death by stimulating the endogenous antioxidant enzymes and inhibiting glutamate-induced oxidative toxicity via the mitophagy–autophagy pathway. TLE might have potential as an alternative or therapeutic approach in neurodegenerative diseases

Ergosterol promotes neurite outgrowth, inhibits amyloid-beta synthesis, and extends longevity: In vitro neuroblastoma and in vivo Caenorhabditis elegans evidence

Aims: Alzheimer's disease (AD), the most common neurodegenerative disorder associated with aging, is characterized by amyloid-beta (A beta) plaques in the hippocampus. Ergosterol, a mushroom sterol, exhibits neuroprotective activities; however, the underlying mechanisms of ergosterol in promoting neurite outgrowth and preventing A beta associated aging have never been investigated. We aim to determine the beneficial activities of ergosterol in neuronal cells and Caenorhabditis elegans (C. elegans). Materials and methods: The neuritogenesis and molecular mechanisms of ergosterol were investigated in wildtype and A beta precursor protein (APP)-overexpressing Neuro2a cells. The anti-amyloidosis properties of ergosterol were determined by evaluating in vitro A beta production and the potential inhibition of A beta-producing enzymes. Additionally, AD-associated transgenic C. elegans was utilized to investigate the in vivo attenuating effects of ergosterol. Key findings: Ergosterol promoted neurite outgrowth in Neuro2a cells through the upregulation of the transmembrane protein Teneurin-4 (Ten-4) mRNA and protein expressions, phosphorylation of the extracellular signal-regulated kinases (ERKs), activity of cAMP response element (CRE), and growth-associated protein-43 (GAP-43). Furthermore, ergosterol enhanced neurite outgrowth in transgenic Neuro2A cells overexpressing either the wild-type APP (Neuro2a-APPwt) or the Swedish mutant APP (Neuro2a-APPswe) through the Ten-4/ ERK/CREB/GAP-43 signaling pathway. Interestingly, ergosterol inhibited A beta synthesis in Neuro2a-APPwt cells. In silico analysis indicated that ergosterol can interact with the catalytic sites of beta- and gamma-secretases. In A beta-overexpressing C. elegans, ergosterol decreased A beta accumulation, increased chemotaxis behavior, and prolonged lifespan. Significance: Ergosterol is a potential candidate compound that might benefit AD patients by promoting neurite outgrowth, inhibiting A beta synthesis, and enhancing longevity

Antioxidant and Anti-Skin Aging Potential of Selected Thai Plants: In Vitro Evaluation and In Silico Target Prediction

The skin is the largest organ that performs a variety of the body’s essential functions. Impairment of skin structure and functions during the aging process might severely impact our health and well-being. Extensive evidence suggests that reactive oxygen species play a fundamental role in skin aging through the activation of the related degradative enzymes. Here, the 16 Thai medicinal plant species were screened for their potential anti-skin aging properties. All extracts were investigated for total phenolic and flavonoid contents, antioxidant, anti-elastase, and anti-tyrosinase activities, as well as the binding ability of compounds with target enzymes by molecular docking. Among all the plants screened, the leaves of A. occidentale and G. zeylanicum exhibited strong antioxidants and inhibition against elastase and tyrosinase. Other potential plants include S. alata leaf and A. catechu fruit, with relatively high anti-elastase and anti-tyrosinase activities, respectively. These results are also consistent with docking studies of compounds derived from these plants. The inhibitory actions were found to be more highly positively correlated with phenolics than flavonoids. Taken together, our findings reveal some Thai plants, along with candidate compounds as natural sources of antioxidants and potent inhibitors of elastase and tyrosinase, could be developed as promising and effective agents for skin aging therapy

Ergosterol isolated from cloud ear mushroom (Auricularia polytricha) attenuates bisphenol A-induced BV2 microglial cell inflammation

© 2022 Elsevier LtdBisphenol A (BPA) has been reported to have neurotoxic properties that may increase the risk of neurodegenerative diseases by inducing neuroinflammation. Auricularia polytricha (AP) is an edible mushroom with several medicinal properties. Herein, the anti-neuroinflammatory effects of AP extracts against BPA-induced inflammation of BV2 microglial cells were investigated. Hexane (APH) and ethanol (APE) extracts of AP inhibited BPA-induced neuroinflammation in BV2 microglia by reducing microglial activation and the expression of pro-inflammatory cytokines. These anti-inflammatory effects were regulated by the NF-κB signaling pathway. In addition, APH and APE exhibited antioxidative effects by increasing the activity of the SOD-1 enzyme and restoring the accumulation of reactive oxygen species (ROS) in BPA-induced BV2 cells. Moreover, the conditioned medium prepared using BPA-induced BV2 cells demonstrated that the presence of APH or APE could attenuate ROS production in HT-22 cells. Further, ergosterol was isolated from APE and also showed anti-inflammatory and antioxidative activities. In conclusion, AP extracts and ergosterol attenuated neuroinflammation against BPA induction in BV2 microglial cells through the NF-κB signaling pathway.N

<i>Aquilaria crassna</i> Leaf Extract Ameliorates Glucose-Induced Neurotoxicity In Vitro and Improves Lifespan in <i>Caenorhabditis elegans</i>

Hyperglycemia is one of the important causes of neurodegenerative disorders and aging. Aquilaria crassna Pierre ex Lec (AC) has been widely used to relieve various health ailments. However, the neuroprotective and anti-aging effects against high glucose induction have not been investigated. This study aimed to investigate the effects of hexane extract of AC leaves (ACH) in vitro using human neuroblastoma SH-SY5Y cells and in vivo using nematode Caenorhabditis elegans. SH-SY5Y cells and C. elegans were pre-exposed with high glucose, followed by ACH treatment. To investigate neuroprotective activities, neurite outgrowth and cell cycle progression were determined in SH-SY5Y cells. In addition, C. elegans was used to determine ACH effects on antioxidant activity, longevity, and healthspan. In addition, ACH phytochemicals were analyzed and the possible active compounds were identified using a molecular docking study. ACH exerted neuroprotective effects by inducing neurite outgrowth via upregulating growth-associated protein 43 and teneurin-4 expression and normalizing cell cycle progression through the regulation of cyclin D1 and SIRT1 expression. Furthermore, ACH prolonged lifespan, improved body size, body length, and brood size, and reduced intracellular ROS accumulation in high glucose-induced C. elegans via the activation of gene expression in the DAF-16/FoxO pathway. Finally, phytochemicals of ACH were analyzed and revealed that β-sitosterol and stigmasterol were the possible active constituents in inhibiting insulin-like growth factor 1 receptor (IGFR). The results of this study establish ACH as an alternative medicine to defend against high glucose effects on neurotoxicity and aging