Hydroxytyrosol Alleviated Hypoxia-Mediated PC12 Cell Damage through Activating PI3K/AKT/mTOR-HIF-1α Signaling.

Background: Hypoxia exerts pressure on cells and organisms, and this pressure can occur under both pathological and nonpathological conditions. There are many reports confirmed that hydroxytyrosol has good in vitro antioxidant activity, while the research about hydroxytyrosol on hypoxia-mediated cell damage is still unclear. Purpose: The aim of this study was to investigate the effect and mechanism of hydroxytyrosol on hypoxia-mediated cell damage. Methods: We studied the effects of hydroxytyrosol on the content of reactive oxygen species, the change of antioxidant enzymes activity of SOD, CAT, and GSH-Px and the content of oxidation products MDA and GSH, and the changes of cell membrane potential and effect on PI3K/AKT/mTOR-HIF-1α signaling pathway under hypoxia-mediated PC12 cell. Results: PC12 cell treated with hydroxytyrosol abated the cell apoptosis and alleviated the oxidative stress through scavenging of reactive oxygen species, improving the enzyme activity and changing the content of oxidation products and alleviating mitochondria damage. Western blotting confirmed that the mechanism maybe related to the PI3K/AKT/mTOR-HIF-1α signaling pathway. The inhibition experiment confirmed that hydroxytyrosol takes part in the expression of protein PI3K and p-mTOR. Conclusion: Hydroxytyrosol reduced the oxidative stress and resisted the inhibition of PI3K/AKT/mTOR-HIF-1α signaling pathway caused by hypoxia, improved cell apoptosis, and ameliorated the antihypoxia ability of PC12 cells under hypoxia.

Effects of Altitude and Duration of Differing Levels of Hypoxic Exposure on Hypoxia-Inducible Factor-1α in Rat Tissues.

Li, Xiao-lin, Wei-gang Wang, Mao-xing Li, Tian-long Liu, Xiu-yu Tian, and Lan Wu. Effects of altitude and duration of differing levels of hypoxic exposure on hypoxia-inducible factor-1α in rat tissues. High Alt Med Biol. 23:173-184, 2022. Objective: This research aimed to evaluate the effects of hypoxia at different altitudes and durations on the expression of hypoxia-inducible factor-1α (HIF-1α) in rat tissues. Methods: A total of 72 Wistar rats were used to investigate the effect of hypoxia at different durations on rat tissues and 72 Wistar rats were used to investigate the effect of hypoxia at different altitudes. Hematoxylin and Eosin (HE) staining was performed to observe the pathological changes of hippocampus tissues, and the expression of HIF-1α of rats under conditions of hypoxia was detected by quantitative real-time polymerase chain reaction and western blotting. Results: According to the pathological results, we found that the degree of the brain, lung, and heart damage and HIF-1α expression, showed an increasing trend as the altitude (1,500, 3,000, 4,500, 6,000, 7,500, and 8,000 m for 12 hours) and duration (0, 6, 12, 24, 36, and 72 hours at 7,500 m) of hypoxia increased. Although there is a significant difference at 8,000 m, considering model stability, animal ethics and cost, we chose 7,500 m as a fixed altitude during hypoxia at different durations. Compared with the normoxic group, the expression of HIF-1α mRNA in the 7,500 m significantly increased by 30.48%, 21.00%, and 12.62%, in brain, lung, and heart tissue (p < 0.01), and HIF-1α mRNA in the 72-hour hypoxic exposure group significantly increased by 52.58%, 20.39%, 27.88% in tissues (p < 0.05). Compared with the normoxic group, HIF-1α protein expressions in the 7,500 m significantly increased by 10.26%, 31.71%, and 13.33% in brain, lung, and heart tissue (p < 0.01, p < 0.01, p < 0.05), and HIF-1α protein expressions in the 72-hour hypoxic exposure group significantly increased by 18.89%, 22.89%, and 29.75% in tissues (p < 0.05). Conclusion: HIF-1α expression in the rat was correlated with altitude and duration of hypoxic exposure.

A review on the structure and pharmacological activity of phenylethanoid glycosides.

Phenylethanoid glycosides (PhGs) are compounds made of phenylethyl alcohol, caffeic acid and glycosyl moieties. The first published references about phenylethanoid glycosides concerned the isolation of echinacoside from Echinaceu ungustifolia (Asteraceae) in 1950 and verbascoside from Verbascum sinuatum (Scrophulariaceae) in 1963. Over the past 60 years, many compounds with these structural characteristics have been isolated from natural sources, and most of these compounds possess significant bioactivities, including antibacterial, antitumor, antiviral, anti-inflammatory, neuro-protective, antioxidant, hepatoprotective, and immunomodulatory activities, among others. In this review, we will summarize the phenylethanoid glycosides described in recent papers and list all the compounds that have been isolated over the past few decades. We will also attempt to present and assess recent studies about the separation, extraction, determination, and pharmacological activity of the excellent natural components, phenylethanoid glycosides.

Crocetin: A Systematic Review.

Crocetin is an aglycone of crocin naturally occurring in saffron and produced in biological systems by hydrolysis of crocin as a bioactive metabolite. It is known to exist in several medicinal plants, the desiccative ripe fruit of the cape jasmine belonging to the Rubiaceae family, and stigmas of the saffron plant of the Iridaceae family. According to modern pharmacological investigations, crocetin possesses cardioprotective, hepatoprotective, neuroprotective, antidepressant, antiviral, anticancer, atherosclerotic, antidiabetic, and memory-enhancing properties. Although poor bioavailability hinders therapeutic applications, derivatization and formulation preparation technologies have broadened the application prospects for crocetin. To promote the research and development of crocetin, we summarized the distribution, preparation and production, total synthesis and derivatization technology, pharmacological activity, pharmacokinetics, drug safety, drug formulations, and preparation of crocetin.

Gardenia jasminoides Ellis: Ethnopharmacology, phytochemistry, and pharmacological and industrial applications of an important traditional Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Gardenia jasminoides Ellis is a popular shrub in the Rubiaceae family. The desiccative ripe fruits of this plant (called Zhizi in China) are well known and frequently used not only as an excellent natural colourant, but also as an important traditional medicine for the treatment of different diseases, such as reducing fire except vexed, clearing away heat evil, and cooling blood and eliminating stasis to activate blood circulation. It has also been declared as the first batch of dual-purpose plants used for food and medical functions in China. AIM OF THE STUDY: This review aims to provide a critical and systematic summary of the traditional uses, ethnopharmacology, phytochemistry, pharmacology, toxicity and industrial applications of Gardenia jasminoides Ellis and briefly proposes several suggestions for future application prospects. MATERIALS AND METHODS: The related information on Gardenia jasminoides Ellis was obtained from internationally recognized scientific databases through the Internet (PubMed, CNKI, Google Scholar, Baidu Scholar, Web of Science, Medline Plus, ACS, Elsevier and Flora of China) and libraries. RESULTS: Approximately 162 chemical compounds have been isolated and identified from this herb. Among them, iridoid glycosides and yellow pigment are generally considered the main bioactive and characteristic ingredients. Various pharmacological properties, such as a beneficial effect on the nervous, cardiovascular and digestive systems, hepatoprotective activity, antidepressant activity, and anti-inflammatory activity, were also validated in vitro and in vivo. Moreover, geniposide and genipin are the most important iridoid compounds isolated from Gardenia jasminoides Ellis, and genipin is the aglycone of geniposide. As the predominant active ingredient with a distinct pharmacological activity, genipin is also an outstanding biological crosslinking agent. Gardenia yellow pigment has also been widely used as an excellent natural dye-stuff. Hence, Gardenia jasminoides Ellis has been applied to many other fields, including the food industry, textile industry and chemical industry, in addition to its predominant medicinal uses. CONCLUSIONS: According to this review, Gardenia jasminoides Ellis is outstanding traditional medical plant used in medicine and food. Pharmacological investigations support the traditional use of this herb and may validate the folk medicinal use of Gardenia jasminoides Ellis to treat different diseases. Iridoid glycosides are potential medicines. Gardenia yellow pigment has been the most important source of a natural colourant for food, cloth and paint for thousands of years. This herb has made great contributions to human survival and development. Moreover, it has also achieved outstanding progress in human life and even in art. Although Gardenia jasminoides Ellis has extremely high and comprehensive utilization values, it is still far from being completely explored. Therefore, the comprehensive development of Gardenia jasminoides Ellis deserves further analysis.

Polysaccharide extracted from Potentilla anserina L ameliorate acute hypobaric hypoxia-induced brain impairment in rats.

High altitude cerebral edema (HACE) is a high altitude malady caused by acute hypobaric hypoxia (AHH), in which pathogenesis is associated with oxidative stress and inflammatory cytokines. Potentilla anserina L is mainly distributed in Tibetan Plateau, and its polysaccharide possesses many physiological and pharmacological properties. In the present study, the protective effect and potential treatment mechanism of Potentilla anserina L polysaccharide (PAP) in HACE were explored. First, we measured the brain water content and observed the pathological changes in brain tissues, furthermore, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione (GSH) were evaluated by kits. Finally, the protein contents and mRNA expressions of pro-inflammatory (IL-1ß, IL-6, TNF-α, vascular endothelial cell growth factor [VEGF], NF-κB, and hypoxia inducible factor-1 α [HIF-1α]) were detected by ELISA kits, RT-PCR, and western blotting. The results demonstrated that PAP reduced the brain water content, alleviated brain tissue injury, reduce the levels of MDA and NO, and increased the activity of SOD and GSH level. In addition, PAP blocking the NF-κB and HIF-1α signaling pathway activation inhibited the generation of downstream pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, and VEGF). Therefore, PAP has a potential to treat and prevent of HACE by suppression of oxidative stress and inflammatory response.

Isolation of 11,12- seco-Rifamycin W Derivatives Reveals a Cleavage Pattern of the Rifamycin Ansa Chain.

This study reported the isolation and characterization of 11 rifamycin congeners including six new ones (1-6) from the agar fermentation extract of Amycolatopsis mediterranei S699. Compounds 1 and 2 are rifamycin glycosides named as rifamycinosides A and B, respectively. Their polyketide skeleton represents a novel cleavage pattern of the rifamycin ansa chain. Compounds 6 and 8 showed potential T3SS inhibitory activity, and 6 induced G2/M phase arrest and caused DNA damage in HCT116 cells.