Effects of rosmarinic acid on immunoregulatory activity and hepatocellular carcinoma cell apoptosis in H22 tumor-bearing mice

Rosmarinic acid (RA) is a natural polyphenolic compound that exists in many medicinal species of Boraginaceae and Lamiaceae. The previous studies have revealed that RA had therapeutic effects on hepatocellular carcinoma (HCC) in the H22-xenograft models by inhibiting the inflammatory cytokines and NF-κB p65 pathway in the tumor microenvironment. However, its molecular mechanisms of immunoregulation and pro-apoptotic effect in HCC have not been fully explored. In the present study, RA at 75, 150, and 300 mg/kg was given to H22 tumor-bearing mice via gavage once a day for 10 days. The results showed that RA can effectively inhibit the tumor growth through regulating the ratio of CD4⁺/CD8⁺ and the secretion of interleukin (IL)-2 and interferon-γ, inhibiting the expressions of IL-6, IL-10 and signal transducer and activator of transcription 3, thereby up-regulating Bax and Caspase-3 and down-regulating Bcl-2. The underlying mechanisms involved regulation of immune response and induction of HCC cell apoptosis. These results may provide a more comprehensive perspective to clarify the anti-tumor mechanism of RA in HCC.

Effect and mechanism of vitamin D combined with puerarin on rat liver fibrosis induced by CCl4 / 重庆医学

Objective To explore the protective effect and mechanism of vitamin D combined with puerarin on liver fibrosis.Methods The rats were divided into normal control group (C),tetrachloromethone group (CCl4),vitamin D group (V),puerarin group(P) and vitamin D combined with puerarin group(V+P).After 8 weeks,the rats were sacrificed and blood and liver samples were collected.The level of blood hyaluronic acid(HA) was tested.The hydroxyproline(Hyp) level in the liver was measured.The liver paraffin sections were made and examined by the sirius red staining.The mRNA levels of collagen Ⅰ and collagen Ⅲ in the liver tissue were detected by RT-PCR,and the levels of NF-κB and TNF-α in the liver were detected by Western blot.Results The CCl4 group appeared obvious liver fibrosis.The liver fibrosis degree was significantly improved in the group V,P and V+P,the blood HA level and liver Hyp level were reduced.The mRNA levels of collagen Ⅰ and collagen Ⅲ as well as the protein levels of NF-κB and TNF-α in the liver were significantly decreased.Among them.The liver fibrosis improvement degree in the V+P group was most significant.Conclusion Vitamin D combined with puerarin can protect rat liver fibrosis induced by CCl4 and its mechanism may be related with reducing the activation of hepatic stellate cells(HSC) and decreasing the collagenous fibers secretion.