Study on anti-inflammatory effect of Shangkehuangshui in vitro and in vivo based on TLR4/TLR2-NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Shangkehuangshui (SK) has been traditionally used to treat traumatic injury, soft tissue and bone injury in Foshan hospital of traditional Chinese medicine for more than 60 years, which composed of many Chinese herbs such as Coptis chinensis Franch., Gardenia jasminoides Ellis, Phellodendron chinense Schneid. and etc. SK exhibits heat-clearing and detoxifying, enhancing blood circulation to eliminate blood stasis properties, and demonstrates noteworthy clinical efficacy. Nevertheless, the underlying mechanism remains uncertain. AIM OF THE STUDY: The early study found that SK had good anti-inflammatory effects in acute soft tissue injury model. This research is to verify the anti-inflammatory properties of SK both in vitro and in vivo via TLR4/TLR2-NF-κB signaling pathway, to clarify the underlying mechanisms responsible for the curative effect of SK. METHODS: The RAW264.7 cells inflammatory model was established with lipopolysaccharide (LPS) in vitro. NO and TNF-α, IL-6, IL-1ß were determined with Griess method and ELISA method respectively. The mRNA and protein expression levels of TLR4/TLR2-NF-κB pathway were evaluated by qPCR and Western blot method. In vivo experiment, chronic soft tissue injury rat models were established by tracking gastrocnemius muscle with electrical stimulation, then local appearance and pathological changes were observed and recorded, the contents of inflammatory factors in serum and tissue were performed. Moreover, we also measured and contrasted the expression of TLR4/TLR2-NF-κB related factors. RESULTS: SK effectively inhibited the LPS-induced generation of inflammatory cytokines, including NO, TNF-α, IL-6 and IL-1ß in RAW264.7 cells, and significantly suppressed the expression of TLR4, TLR2, MyD88, IκB, and NF-κB. In vivo, SK remarkably decreased the damage appearance scores after 4 and 14 days of administration and inhibit the quantity of NO and leukocytes present in the serum. Additionally, the inflammatory infiltration in the pathological section was alleviated, myofibrillar hyperplasia and blood stasis were reduced. SK markedly downregulated NO, TNF-α, IL-6 and IL-1ß in injured tissues of rats, also declined the expression of TLR4, TLR2, MyD88, IκB, NF-κB, IL-6, TNF-α and IL-1ß. CONCLUSION: This study revealed that SK had obvious effects of anti-inflammatory actions in vivo and vitro, effectively reduced acute and chronic soft tissue injury in clinical, this might be attributed to inhibit the TLR4/TLR2-NF-κB pathway, further inhibit the expression of downstream relevant pro-inflammatory cytokines.

Curcumin and Its Analogs in Non-Small Cell Lung Cancer Treatment: Challenges and Expectations.

Researchers have made crucial advances in understanding the pathogenesis and therapeutics of non-small cell lung cancer (NSCLC), improving our understanding of lung tumor biology and progression. Although the survival of NSCLC patients has improved due to chemoradiotherapy, targeted therapy, and immunotherapy, overall NSCLC recovery and survival rates remain low. Thus, there is an urgent need for the continued development of novel NSCLC drugs or combination therapies with less toxicity. Although the anticancer effectiveness of curcumin (Cur) and some Cur analogs has been reported in many studies, the results of clinical trials have been inconsistent. Therefore, in this review, we collected the latest related reports about the anti-NSCLC mechanisms of Cur, its analogs, and Cur in combination with other chemotherapeutic agents via the Pubmed database (accessed on 18 June 2022). Furthermore, we speculated on the interplay of Cur and various molecular targets relevant to NSCLC with discovery studio and collected clinical trials of Cur against NSCLC to clarify the role of Cur and its analogs in NSCLC treatment. Despite their challenges, Cur/Cur analogs may serve as promising therapeutic agents or adjuvants for lung carcinoma treatment.

Pharmacological Mechanisms of Shangke Huangshui against Skin and Soft Tissue Infection.

BACKGROUND: Skin and soft tissue infections (SSTIs) are a group of common diseases, usually caused by bacteria. Shangke Huangshui (SK) has been widely used to treat various SSTIs diseases for many years, but its mechanism is unclear. Therefore, this study was designed to investigate the anti-infective effect of SK on different skin and soft tissue infection diseases and to explore its underlying mechanism. METHODS: The subcutaneous abscess mouse model, the dermal ulcer rat model, and the infectious soft tissue injury rat model were established by injection of Staphylococcus aureus to evaluate the anti-inflammatory and antibacterial effects of SK. Abscess volume, local appearance score and histological changes, bacterial contents, and hydroxyproline concentration in the skin or soft tissue were analyzed. The levels of NO, TNF-α, IL-1ß, and IL-8 in the serum and tissue were determined by ELISA method. The mRNA expression levels of TLR2, MyD88, TAK1, NF-κB, AP-1, and other genes were measured with qRT-PCR method, and the protein expression of TLR2, MyD88, TAK1, NF-κB, and AP-1 was detected by western blot method. RESULTS: SK had an obvious therapeutic effect on skin and soft tissue infections. It reduced the volume of abscess and promoted the healing of skin ulcer, improved pathological phenomena, such as inflammatory infiltration of skin and soft tissue, reduced the levels of white blood cells and NO in the blood, decreased bacteria contents in the skin and soft tissue. Furthermore, SK decreased the mRNA expression of TLR2, MyD88, TAK1, NF-κB and AP-1, and other related genes and also downregulated the protein expression of TLR2, MyD88, TAK1, NF-κB, and AP-1. CONCLUSION: The experiments provide evidence that SK can treat skin and soft tissue infection diseases based on its comprehensive antibacterial and anti-inflammatory effects. The therapeutic mechanism may be associated with the inhibition of TLR2/MyD88/NF-κB signaling pathway.