Gegen Qinlian pills alleviate carrageenan-induced thrombosis in mice model by regulating the HMGB1/NF-κB/NLRP3 signaling.

BACKGROUND: The high incidence of thrombotic events is one of the clinical characteristics of coronavirus disease of 2019 (COVID-19), due to a hyperinflammatory response caused by the virus. Gegen Qinlian Pills (GQP) is a Traditional Chinese Medicine that is included in the Chinese Pharmacopoeia and played an important role in the clinical fight against COVID-19. Although GQP has shown the potential to treat thrombosis, there is no relevant research on its treatment of thrombosis so far. HYPOTHESIS: We hypothesized that GQP may be capable inhibit inflammation-induced thrombosis. STUDY DESIGN: We tested our hypothesis in a carrageenan-induced thrombosis mouse model in vivo and lipopolysaccharide (LPS)-induced human endothelial cells (HUVECs) in vitro. METHODS: We used a carrageenan-induced mouse thrombus model to confirm the inhibitory effect of GQP on inflammation-induced thrombus. In vitro, studies in human umbilical vein endothelial cells (HUVECs) and in silico network pharmacology analyses were performed to reveal the underlying mechanisms of GQP and determine the main components, targets, and pathways of GQP, respectively. RESULTS: Oral administration of 227.5 mg/kg, 445 mg/kg and 910 mg/kg of GQP significantly inhibited thrombi in the lung, liver, and tail and augmented tail blood flow of carrageenan-induced mice with reduced plasma tumor necrosis factor α (TNF-α) and diminished expression of high mobility group box 1 (HMGB1) in lung tissues. GQP ethanol extract (1, 2, or 5 µg/ml) also reduced the adhesion of platelets to LPS stimulated HUVECs. The TNF-α and the expression of HMGB1, nuclear factor kappa B (NF-κB), and NLR family pyrin domain containing 3 (NLRP3) in LPS stimulated HUVECs were also attenuated. Moreover, we analyzed the components of GQP and inferred the main targets, biological processes, and pathways of GQP in the treatment of inflammation-induced thrombosis through network pharmacology. CONCLUSION: Overall, we demonstrated that GQP could reduce inflammation-induced thrombosis by inhibiting HMGB1/NFκB/NLRP3 signaling and provided an accurate explanation for the multi-target, multi-function mechanism of GQP in the treatment of thromboinflammation, and provides a reference for the clinical usage of GQP.

A comprehensive review of herbacetin: From chemistry to pharmacological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbacetin is an active constituent of traditional Chinese medicines such as Ephedra sinica Stapf (MaHuang) and Sedum roseum (L.). Scop. (Hong JingTian). MaHuang was used to treat cough, asthma, fever, and edema for more than 5000 years, while Hong JingTian was used to treat depression, fatigue, cancers, and cardiovascular disease. Recent studies indicate that herbacetin and its glycosides play a critical role in the pharmacological activities of these herbs. However, currently, no comprehensive review on herbacetin has been published yet. AIM OF THE STUDY: This review aimed to summarize information on the chemistry, natural sources, and pharmacokinetic features of herbacetin, with an emphasis on its pharmacological activities and possible mechanisms of action. MATERIALS AND METHODS: A literature search was performed on the Web of Science, PubMed, and China Knowledge Resource Integrated databases (CNKI) using the search term "herbacetin" ("all fields") from 1935 to 2020. Information was also obtained from classic books of Chinese herbal medicine, Chinese pharmacopeia, and the database "The Plant List" (www.theplantlist.org). Studies have been analyzed and summarized in this review if they dealt with chemistry, taxonomy, pharmacokinetic, and pharmacological activity. RESULTS: Herbacetin is distributed in various plants and can be extracted or synthesized. It showed diverse pharmacological activities including antioxidant, antiviral, anti-inflammatory, anticancer, antidiabetic, and anticholinesterase. It is thought to have great potential in cancer treatment, especially colon and skin cancers. However, the bioavailability of herbacetin is low and the toxicity of herbacetin has not been studied. Thus, more studies are required to solve these problems. CONCLUSIONS: Herbacetin shows promising pharmacological activities against multiple diseases. Future research should focus on improving bioavailability, further studying its pharmacological mechanism, evaluating its toxicity and optimal dose, and performing the clinical assessment. We hope that the present review will serve as a guideline for future research on herbacetin.