PHYTOCHEMISTRY
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2018
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IF 3.186
Xing-Long Chen,Fang Liu,Xue-Rong Xiao,Xiu-Wei Yang,Fei Li
Tripterygium hypoglaucum (H. Lév.) Hutch. has been used to remedy rheumatoid arthritis , however, it shows frequent toxicity to the body. In this study, liquid chromatograph-mass spectrometer (LC-MS) was guided to characterize abietanes diterpenoids with anti-inflammatory activity from the stem of T. hypoglaucum . Thirteen undescribed abietanes diterpenoids were isolated and purified, and their chemical structure was identified using various spectroscopic methods . These compounds belonged to abietanes with splitting C ring, abietanes with benzenoid rings, diterpene quinoids , diterpene quinoids with lactone rings, and abietanes with benzenoid and lactone rings, respectively. Lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages was used to evaluate anti-inflammatory activity of the compounds. The results indicated that hypoglicin B-G and hypoglicin J-M exhibited inhibitory activity of NO production with the IC 50 values of 6.01, 25.21, 8.29, 3.63, 0.72, 0.89, 36.91, 0.82, 2.85, 11.92 μM, respectively. Among these compounds, compound hypoglicin L showed high anti-inflammatory activity and low toxicity (SI = 5.02 × 10 4 ). Further QPCR analysis revealed that hypoglicin D and hypoglicin L can inhibit the mRNA expression of iNOS in LPS-stimulated RAW264.7 cells at doses of 12.5 and 3.13 μM, respectively. Taken together, ten anti-inflammatory diterpenoids were found from T. hypoglaucum in this study.
研究领域:
药理学
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植物化学
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Yumei Sun,Jihong Wang,Peiyao Hu,Yi Tang,Yanwen Wang,Jianzhou Ye,Xuesong Yang,Junlin Yin
Tripterygium hypoglaucum (Lévl.) Hutch rhizome (THH) is mainly used in the clinical setting for the treatment of autoimmune diseases such as rheumatoid arthritis. In total, four active compounds were isolated from THH methanol extract （THH-MeOH）and identified. The HPLC results showed that the proportions of the active ingredients in THH-MeOH (i.e., celastrol, triptolide, and 3- O -acetyloleanolic acid) were 0.79 ‰, 0.46 ‰, and 0.76 ‰, respectively. THH-MeOH attenuated the M5-induced hyperproliferation of HaCaT cells, decreased the mRNA expression levels of inflammatory cytokines, and inhibited the phosphorylation of I κ B α , NF- κ B p65, MAPK, and STAT3/JAK2. Furthermore, THH-MeOH significantly reduced PASI scores in mice; reduced the level of Ki67 expression in skin tissues; decreased the expression of inflammatory cytokines in the skin lesions and serum; and ameliorated the IMQ-induced imbalance in the ROR γ t / Foxp3 ratio. The extract can attenuate psoriasis-like lesions by inhibiting cellular hyperproliferation, ameliorating inflammatory reactions, and modulating immune responses. Our work provides a theoretical basis to support the use of THH for treating psoriasis.
研究领域:
药理学
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免疫学
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皮肤科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
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2023
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IF 4.6
Jianghui HU,Jimin NI,Junping ZHENG,Yanlei GUO,Yong YANG,Cheng YE,Xiongjie SUN,Hui XIA,Yanju LIU,Hongtao LIU
Traditionally, Tripterygium hypoglaucum (Levl.) Hutch (THH) are widely used in Chinese folk to treat rheumatoid arthritis (RA). This study aimed to investigate whether the anti-RA effect of THH is related with the gut microbiota. The main components of prepared THH extract were identified by HPLC-MS. C57BL/6 mice with adjuvant-induced arthritis (AIA) were treated with THH extract by gavage for one month. THH extract significantly alleviated swollen ankle, joint cavity exudation, and articular cartilage destruction in AIA mice. The mRNA and protein levels of inflammatory mediators in muscles and plasma indicated that THH extract attenuated inflammatory responses in the joint by blocking TLR4/MyD88/MAPK signaling pathways. THH extract remarkably restored the dysbiosis of the gut microbiota in AIA mice, featuring the increases of Bifidobacterium , Akkermansia , and Lactobacillus and the decreases of Butyricimonas , Parabacteroides , and Anaeroplasma . Furthermore, the altered bacteria were closely correlated with physiological indices and drove metabolic changes of the intestinal microbiota. In addition, antibiotic-induced pseudo germ-free mice were employed to verify the role of the intestinal flora. Strikingly, THH treatment failed to ameliorate the arthritis symptoms and signaling pathways in pseudo germ-free mice, which validates the indispensable role of the intestinal flora. For the first time, we demonstrated that THH extract protects joint inflammation by manipulating the intestinal flora and regulating the TLR4/MyD88/MAPK signaling pathway. Therefore, THH extract may serve as a microbial modulator to recover RA in clincial practice.ver RA in clincial practice.
研究领域:
药理学
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免疫学
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微生物学
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风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Junping Zheng,Jianghui Hu,Yong Yang,Lei Xiong,Huabing Yang,Zhigang Zhang,Nan Jiang,Hongtao Liu
Tripterygium hypoglaucum (Levl.) Hutch (THH) has long been used as a remedy for rheumatoid arthritis (RA) in China. However, it is unclear whether the anti-RA mechanism of THH is associated with inflammasome or gut-joint axis. In this study, we aimed to explore the critical role of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and bile acid (BA) in the anti-RA mechanism. Complete Freund’s adjuvant (CFA)-injected mice were treated with THH extract (250 mg/kg/d) for 35 days, and joint swelling and disease scores were measured. After THH treatment, the joint swelling and RA disease score in CFA-treated mice significantly subsided. The increased ratios of lymphocytes, monocytes, and white blood cells were attenuated by THH treatment. Notably, THH treatment blocked the inflammation in both joints and colons by suppressing the NLRP3-mediated inflammasome, as indicated by NLRP3, interleukin 1beta (IL-1β), and Caspase-1. Meanwhile, THH significantly remodeled the bile acid (BA) profiles in RA mice. Spearman’s analysis shed light on the close link between BAs, NLRP3 inflammasome, and RA indicators. However, THH treatment failed to improve inflammasome activation, snoptivis, and joint swelling in RA mice with gut microbiota depletion. In summary, we revealed the pivotal role of BA-mediated gut-joint axis and inflammasome in THH’s RA amelioration. In the future, more work should be done to explain the in-depth mechanism between altered BAs and inflammasome.
研究领域:
药理学
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免疫学
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风湿病学
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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