It has been widely recognized that inflammation, particularly chronic inflammation, can increase the risk of cancer and that the simultaneous treatment of inflammation and cancer may produce excellent therapeutic effects. Berberine, an alkaloid isolated from Rhizoma coptidis, has broad applications, particularly as an antibacterial agent in the clinic with a long history. Over the past decade, many reports have demonstrated that this natural product and its derivatives have high activity against both cancer and inflammation. In this review, we summarize the advances in studing berberine and its derivatives as anti-inflammatory and anti-tumor agents in the digestive system; we also discuss their structure-activity relationship. These data should be useful for the development of this natural product as novel anticancer drugs with anti-inflammation activity.

As our ongoing research project on Ban Lan Gen (Isatis tinctoria roots), a total of 23 alkaloids were obtained. Compounds 1 and 2 contain an unusual C–C bond between the 2(1H)-quinolinone moiety and the phenol moiety and between the 2(1H)-quinolinone moiety and the 1H-indole moiety, respectively. Compound 3 possesses an unusual carbon skeleton and its putative biosynthetic pathway was discussed, and Compound 23 was deduced as a new indole alkaloid glycoside. Compounds 4–7 were identified as four new natural products by extensive spectroscopic experiments. Additionally, the anti-inflammatory activity was assessed based on nitric oxide (NO) production using Lipopolysaccharide-stimulated RAW264.7 macrophages. Compounds 9, 15, and 17 showed inhibitory effects with IC₅₀ values of 1.2, 5.0, and 74.4 μM.

Cinnamon barks extracts have been reported to regulate immune function; however, the component(s) in cinnamon barks responsible for this effect is/are not yet clear. The aim of this study is to find out the possible component(s) that can be used as therapeutic agents for immune‐related diseases from cinnamon bark. In this study, the immunosuppressive effects of fraction (named CT‐F) and five procyanidin oligomers compounds, cinnamtannin B1, cinnamtannin D1 (CTD‐1), parameritannin A1, procyanidin B2, and procyanidin C1, from Cinnamomum tamala or Cinnamomum cassia bark were examined on splenocytes proliferation model induced by ConA or LPS. Then, the effects of activated compound CTD‐1 on cytokine production and 2,4‐dinitrofluorobenzene (DNFB) induced delayed‐type hypersensitivity (DTH) response were detected to evaluate the immunosuppressive activity of CTD‐1. It was found that CT‐F and CTD‐1 significantly inhibited the splenocyte proliferation induced by ConA or LPS. CTD‐1 dose‐dependently reduced the level of IFN‐γ and IL‐2 and intensively suppressed DNFB‐induced DTH responses. These findings suggest that the immunosuppressive activities of cinnamon bark are in part due to procyanidin oligomers. CTD‐1 may be a potential therapeutic agent for immune‐related diseases.

This study investigated the possible enhancement of berberine’s (BB) hypoglycemic activity by oligomeric proanthocyanidins (OPCs) and its underlying mechanism. The hypoglycemic activity of the studied compounds was evaluated in diabetic db/db mice. The cellular uptake and efflux of BB with or without OPCs were investigated using Caco-2 intestinal cells. A pharmacokinetic study of BB and OPCs was performed in Sprague Dawley (SD) mice by oral administration of the study compounds. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) was employed to determine the cellular efflux, retention, and the serum concentrations of the compounds. The results revealed that OPCs considerably potentiated the hypoglycemic efficacy of BB in diabetic db/db mice. In the in vitro experiments, OPCs significantly inhibited the efflux and increased the uptake of the P-glycoprotein (P-gp) substrate rhodamine-123 (R123) and BB in Caco-2 intestinal cells. Moreover, OPCs substantially reduced the expression of P-gp in Caco-2 cells. The inhibition of BB efflux by OPCs was translated into the improved pharmacokinetics in vivo. When co-administered, OPCs obviously increased the average maximum concentration of BB in mice. In summary, this study demonstrated that combination of BB with OPCs could significantly improve the pharmacokinetics and hypoglycemic efficacy of BB, which is valuable for future exploration of the combination of BB and OPCs as oral hypoglycemic agents.