Gelsevirine improves age-related and surgically induced osteoarthritis in mice by reducing STING availability and local inflammation

Feng, Meixia; Kong, De-Pei; Guo, Huan; Xing, Chunlei; Lv, Juan; Bian, Huihui; Lv, Nanning; Zhang, Chenxi; Chen, Dagui; Liu, Mingming; Yu, Yongsheng; Su, Li

doi:10.1016/j.bcp.2022.114975

Cited by 25 publications

(23 citation statements)

References 25 publications

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“…, every 3 days for 10 weeks) could markedly reduce OARSI scores and MMP13 expression levels and increased cartilage area and Col2A expression levels in STING-deficient mice and the destabilisation of the medial meniscus-operated mice. Its latent mechanism was in conformity with the promotion of the K48-ubiquitination of STING 59 . Recent studies on collagen-induced rats of arthritis disclosed that treatment with koumine ( 2 ) alone (0.6, 3.0, or 15.0 mg/kg, i.g.…”

Section: Pharmacological Activitymentioning

confidence: 57%

Recent progress in chemistry and bioactivity of monoterpenoid indole alkaloids from the genus gelsemium : a comprehensive review

Wang

Chen

Gao³

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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Monoterpenoid indole alkaloids (MIAs) represent a major class of active ingredients from the plants of the genus Gelsemium . Gelsemium MIAs with diverse chemical structures can be divided into six categories: gelsedine-, gelsemine-, humantenine-, koumine-, sarpagine- and yohimbane-type. Additionally, gelsemium MIAs exert a wide range of bioactivities, including anti-tumour, immunosuppression, anti-anxiety, analgesia, and so on. Owing to their fascinating structures and potent pharmaceutical properties, these gelsemium MIAs arouse significant organic chemists’ interest to design state-of-the-art synthetic strategies for their total synthesis. In this review, we comprehensively summarised recently reported novel gelsemium MIAs, potential pharmacological activities of some active molecules, and total synthetic strategies covering the period from 2013 to 2022. It is expected that this study may open the window to timely illuminate and guide further study and development of gelsemium MIAs and their derivatives in clinical practice.

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Section: Pharmacological Activitymentioning

confidence: 57%

Recent progress in chemistry and bioactivity of monoterpenoid indole alkaloids from the genus gelsemium : a comprehensive review

Wang

Chen

Gao³

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…The membranes were visualized using the Image Lab 3.0 software (BioRad). Specific primary antibodies against stimulator of interferon genes (STING) (no 13647), p-TBK1 (ser172; no 5483), p-p65 (ser536; no 3033), and GAPDH (no 5174) were obtained from Cell Signaling Technology (Danvers, MA, USA) …”

Section: Methodsmentioning

confidence: 99%

“…Raw264.7 cells were pretreated with tested compounds (20 μM) for 2 h and then stimulated with DMXAA (25 μg/mL) for 1 h. Total RNA was isolated from RAW264.7 cells using triazole reagent (Thermo Fisher Scientific). 9 Synthesis of cDNA was carried out with SuperScript III reverse transcriptase (Invitrogen). Realtime PCR was conducted with a PrimeScript RT reagent kit (Takara).…”

Section: General Materials and Experimentalmentioning

confidence: 99%

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Anti-inflammatory Oleanane-Type Triterpenoids Produced by Nonomuraea sp. MYH522 through Microbial Transformation

Chen

Zhi

et al. 2023

J. Agric. Food Chem.

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Eleven oleanane-type triterpenoids named soyasapogenols B1–B11 have been obtained unexpectedly from a marine actinomycete Nonomuraea sp. MYH522. Their structures have been determined by extensive analysis of spectroscopic experiments and X-ray crystallographic data. Soyasapogenols B1–B11 exhibit subtle differences in the positions and degrees of oxidation on an oleanane skeleton. The feeding experiment suggested that soyasapogenols might be derived from soyasaponin Bb through microbial-mediated conversion. The biotransformation pathways from soyasaponin Bb to five oleanane-type triterpenoids and six A-ring cleaved analogues were proposed. The assumed biotransformation involves an array of reactions including regio- and stereo-selective oxidation. These compounds alleviated the 5,6-dimethylxanthenone-4-acetic acid-induced inflammation in Raw264.7 cells via the stimulator of interferon genes/TBK1/NF-κB signaling pathway. The present work provided an efficient approach for rapid diversification of soyasaponins and for developing food supplements with potent anti-inflammatory effects.

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“…Gelsevirine (Gs), an alkaloid from Gelsemium elegans , has a novel hexacyclic cage structure and a favorable safety profile. Gs improves age-related and surgically induced osteoarthritis in mice by reducing local inflammation ( 20 ). The potential ability to decrease inflammation makes Gs possible to be used in treating other inflammation-related diseases in the central nervous system, such as neurodegenerative diseases and stroke.…”

Section: Introductionmentioning

confidence: 99%

Regulation of microglia related neuroinflammation contributes to the protective effect of Gelsevirine on ischemic stroke

Xing

Zhu

et al. 2023

Front. Immunol.

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Stroke, especially ischemic stroke, is an important cause of neurological morbidity and mortality worldwide. Growing evidence suggests that the immune system plays an intricate function in the pathophysiology of stroke. Gelsevirine (Gs), an alkaloid from Gelsemium elegans, has been proven to decrease inflammation and neuralgia in osteoarthritis previously, but its role in stroke is unknown. In this study, the middle cerebral artery occlusion (MCAO) mice model was used to evaluate the protective effect of Gs on stroke, and the administration of Gs significantly improved infarct volume, Bederson score, neurobiological function, apoptosis of neurons, and inflammation state in vivo. According to the data in vivo and the conditioned medium (CM) stimulated model in vitro, the beneficial effect of Gs came from the downregulation of the over-activity of microglia, such as the generation of inflammatory factors, dysfunction of mitochondria, production of ROS and so on. By RNA-seq analysis and Western-blot analysis, the JAK-STAT signal pathway plays a critical role in the anti-inflammatory effect of Gs. According to the results of molecular docking, inhibition assay, and thermal shift assay, the binding of Gs on JAK2 inhibited the activity of JAK2 which inhibited the over-activity of JAK2 and downregulated the phosphorylation of STAT3. Over-expression of a gain-of-function STAT3 mutation (K392R) abolished the beneficial effects of Gs. So, the downregulation of JAK2-STAT3 signaling pathway by Gs contributed to its anti-inflammatory effect on microglia in stroke. Our study revealed that Gs was benefit to stroke treatment by decreasing neuroinflammation in stroke as a potential drug candidate regulating the JAK2-STAT3 signal pathway.

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Gelsevirine improves age-related and surgically induced osteoarthritis in mice by reducing STING availability and local inflammation

Cited by 25 publications

References 25 publications

Recent progress in chemistry and bioactivity of monoterpenoid indole alkaloids from the genus gelsemium : a comprehensive review

Recent progress in chemistry and bioactivity of monoterpenoid indole alkaloids from the genus gelsemium : a comprehensive review

Anti-inflammatory Oleanane-Type Triterpenoids Produced by Nonomuraea sp. MYH522 through Microbial Transformation

Regulation of microglia related neuroinflammation contributes to the protective effect of Gelsevirine on ischemic stroke

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