Water-separated part of Chloranthus serratus alleviates lipopolysaccharide- induced RAW264.7 cell injury mainly by regulating the MAPK and Nrf2/HO-1 inflammatory pathways

Li³

et al. 2021

Exp Ther Med

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Chloranthus serratus is a traditional Chinese medicine for treating arthritis and bruises. The aim of the present study was to investigate the anti-arthritic activities and possible associated mechanisms of different isolated sites of Chloranthus serratus (DISC) in adjuvant-induced arthritis (AA) rats. The therapeutic effects of the extracts were assessed through changes in body weights, swelling rates, arthritis indexes (AI) and organ indexes. The levels of nitric oxide (NO), malondialdehyde and superoxide dismutase were determined using one-step method, TBA method and hydroxylamine method, respectively; the levels of TNF-α, IL-1β, IL-6, prostaglandin E 2 , macrophage inhibitor factor-1, VEGF, immunoglobulin (Ig) G, IgM and IFN-γ in serum were determined using ELISA. Pathological changes and positive expression of VEGF in the ankle joints were investigated using hematoxylin-eosin staining and immunohistochemical staining, respectively. DISC treatment increased the weight gains and thymus indexes, and decreased the swelling rates, spleen indexes and AI in AA rats. The water isolated site (WA) and ethyl acetate isolated site (EA) significantly reversed complete Freund's adjuvant (CFA)-induced changes in the levels of NO, IL-6, TNF-α, IgG and IFN-γ, while the n-butanol isolated site (NB) only reversed the changes in IL-6 and IgG contents. Some changes in the chloroform isolated site group showed the same trend as those in the model group. The extracts relieved synovial hyperplasia, inflammatory cell infiltration and articular surface defects, and reduced the positive expression rate of VEGF in the synovial tissues of the AA rats to varying degrees. The WA exhibited the most marked effects, followed by the EA and NB, indicating that WA had optimal therapeutic effects on CFA-induced arthritic rats, which may be mediated by the oxidative stress and inhibition of inflammatory factors. C. serratus may serve as a potential candidate for the treatment of rheumatoid arthritis.

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti‑inflammatory activity of different isolated sites of Chloranthus serratus in complete Freund's adjuvant‑induced arthritic rats

Li³

et al. 2021

Exp Ther Med

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“…The sample solutions were obtained by dissolving 0.05 g of the ER, ES and EL in 75% ethanol to obtain a concentration of 1 mg/mL, respectively. After blank correction with 75% ethanol, the solutions were scanned by using a Hitachi U-5100 spectrophotometer (Hitachi High-Tech Science Corporation, Japan) under the following spectral conditions: data mode: Abs; scanning range: 190-500 nm; scanning speed: 400 nm/min; delay: 0 s; response: fast; sampling interval: 1.0 nm; cycle time: 1.0 min; and slit width: 5.0 nm (Sun et al 2019).…”

Section: Plant Materials Extract Preparation and Uv Fingerprint Analysismentioning

confidence: 99%

“…Previous experiments have shown that the ethanol extract of C. serratus roots has obvious anti-inflammatory activity (Sun and Li 2013). Moreover, the water-extractable components of C. serratus might exert an antiinflammatory effect by inhibiting pro-inflammatory cytokines and mediators in lipopolysaccharide-stimulated macrophages (Sun et al 2019). The evaluation of the therapeutic effect on arthritis in vivo has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effects of the root, stem and leaf extracts of Chloranthus serratus on adjuvant-induced arthritis in rats

Li²,

et al. 2020

Pharmaceutical Biology

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Context: Chloranthus serratus [(Thunb.) Roem. et Schult, (Chloranthaceae)] is a folk medicine used for the treatment of rheumatoid arthritis. Objective: The aim of this study was to investigate anti-arthritic effects of the ethanol extracts of the roots (ER), stems (ES) and leaves (EL) of C. serratus on adjuvant arthritis rats and related mechanisms. Materials and methods: The rats were immunized by intradermal injection of complete Freund's adjuvant (CFA, 0.18 mL) into the right hind feet, and received intragastric administrations of the ER, ES and EL (2.07, 1.61 and 0.58 g/kg/d, respectively) for 14 days. The anti-arthritic activity was assessed by swelling rates, serum indicators, antioxidant capacity, histopathological and immunohistochemical analyses. Results: The LD 50 of the ER, ES and EL was higher than 10.35, 8.05 and 2.90 g/kg/p.o., respectively. Extract treatments decreased swelling rates, tumour necrosis factor-alpha (TNF-a), vascular endothelial growth factor (VEGF), interleukin 1 beta (IL-1b), migration inhibitory factor 1 (MIF-1), immunoglobulin G (IgG) and immunoglobulin M (IgM) levels and positive expression of VEGF in the arthritic rats (p < 0.01 or p < 0.05). The ER significantly decreased NO (3.91 ± 0.61 mmol/L), IL-6 (75.67 ± 16.83 pg/mL) and malondialdehyde (MDA) (2.28 ± 0.32 nmol/mL) contents and clearly increased IFN-c (2082 ± 220.93 pg/mL) and superoxide dismutase (SOD) (601.98 ± 38.40 U/mL) levels. The ES and EL did not reverse the changes in some indicators. All the extracts alleviated inflammatory cell infiltration and synovial cell proliferation. Among them, the ER was the most pronounced. Discussion and conclusions: ER exerts the most promising effects, as shown by inhibiting the releases of inflammatory cytokines and enhancing antioxidant capacity, which provides a scientific basis for further research on C. serratus and its clinical applications.

“…According to the Chinese Medicine Dictionary (NUTCM 2006), C. serratus has many therapeutic effects, including dispelling wind, relieving pain, promoting blood circulation to dissipate blood stasis, and treating injuries from fall, rheumatic pain, and other symptoms. Moreover, the water-extractable components of C. serratus might exert an anti-inflammatory effect in lipopolysaccharide-stimulated macrophages (Sun et al 2019b), and the anti-arthritic activity of different parts of C. serratus in adjuvant arthritis rats is related to inhibiting the release of inflammatory cytokines and improving antioxidant capacity (Sun et al 2020b).…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress-mediated hepatotoxicity in rats induced by ethanol extracts of different parts of Chloranthus serratus

Wang

et al. 2020

Pharmaceutical Biology

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Context: Chloranthus serratus (Thunb.) Roem. et Schult. (Chloranthaceae) is an herb widely used as a folk medicine treating inflammatory diseases, although it is toxic. Objective: To investigate hepatotoxicity and related mechanisms induced by ethanol extracts of different parts of C. serratus in rats. Materials and methods: Sprague Dawley rats were divided into control (Con), ethanol extract of roots (ER), stems (ES), and leaves (EL) groups, and acute oral toxicity studies were conducted. The rats received doses of 4.14, 3.20, and 1.16 g/kg/d extracts for 14 days, respectively. Liver index, liver function and oxidative stress biomarkers, liver pathology, ultrastructure, TNF-a, ICAM-1, and Nrf2/HO-1 proteins expression levels were determined. Results: The LD 50 of ER, ES, and EL were higher than 10.35, 8.05, and 2.90 g/kg/p.o., respectively. The liver indexes in the extract groups increased significantly. EL dramatically increased TP, GLB, AST, ALT, ALP, TBA, MDA, ICAM-1, and TNF-a levels (p < 0.01), and induced the most obvious pathological and ultrastructural changes. ES and EL obviously decreased the T-SOD, GSH, CAT, and CHOL levels. Nrf2 and HO-1 proteins expression was reduced significantly in ES (0.77 ± 0.06, 2.33 ± 0.20) and EL (0.23 ± 0.04, 2.14 ± 0.16) groups, and reduced slightly in ER (1.08 ± 0.10; 3.39 ± 0.21) group. Discussion and conclusion: ES and EL induce stronger hepatotoxicity than ER through oxidative stress and the Nrf2/HO-1 pathway, and the root is a better medicinal part, which provides a basis for clinical research, safe applications, and reasonable development of C. serratus.