A standardized extract of Echinacea purpurea containing higher chicoric acid content enhances immune function in murine macrophages and cyclophosphamide-induced immunosuppression mice.

CONTEXT: Preparations of Echinacea have been used by herbalists to boost the immune system. OBJECTIVE: In this study, Echinacea purpurea (L.) Moench (Asteraceae) extract with enriched chicoric acid content was investigated for immunomodulation. MATERIALS AND METHODS: The standardized hydroalcoholic extract (4% chicoric acid) was prepared from the aerial parts of E. purpurea (SEP). The extract was screened for in vitro antioxidant activities, and immunomodulation in RAW 264.7 cells, at 200 and 400 µg/mL. Further, the male BALB/c mice (20-25 g) were divided into 4 groups (n = 6 per group). All the groups except control, were intraperitoneally injected with 70 mg/kg/day of cyclophosphamide (CTX) for 4 consecutive days. The treatment groups received SEP extract (100 and 200 mg/kg body weight) p.o. from day 5 to 14. RESULTS: The SEP extract inhibited DPPH (IC50 = 106.7 µg/mL), ABTS+ (IC50 = 19.88 µg/mL) and nitric oxide (IC50 = 120.1 µg/mL). The SEP extract's ORAC (oxygen radical absorbance capacity) value was 1931.63 µM TE/g. In RAW 264.7 cells, SEP extract increased the nitric oxide production by 30.76- and 39.07-fold at 200 and 400 µg/mL, respectively, compared to the untreated cells. SEP extract significantly increased phagocytosis and cytokine release (TNF-α, IL-6, and IL-1ß) in the cells. Further, the extract improved immune organ indices, lymphocyte proliferation and serum cytokine levels in CTX-induced mice. The extract at 200 mg/kg significantly increased the natural killer cell activity (24.6%) and phagocytic index (28.03%) of CTX mice. CONCLUSION: Our results strongly support SEP extract with 4% chicoric acid as a functional ingredient for immunomodulation.

Viphyllin™, a standardized extract from black pepper seeds, mitigates intestinal inflammation, oxidative stress, and anxiety-like behavior in DSS-induced colitis mice.

Inflammatory bowel diseases (IBD) are the common health concern in populations across the world. Clinical evidence suggests that IBD, characterized by intestinal inflammation, is associated with neuronal manifestations to a greater extent. In this study, we have investigated the protective effects of Viphyllin™, a standardized black pepper (Piper nigrum) seed extract containing 30% ß-caryophyllene against dextran sodium sulfate (DSS)-induced colitis in mice. Oral pretreatment of Viphyllin at the 50 mg and 100 mg/kg doses significantly reversed the clinical symptoms of colitis in mice. Viphyllin markedly inhibited NLRP3 inflammasome activation and improved barrier function in colon tissue. Viphyllin further mitigated the DSS-induced anxiety-like behavior in mice. Interestingly, Viphyllin improved brain antioxidant status and promoted neuronal cell survival in colitis model mice. In conclusion, our findings strongly support the health claims of Viphyllin as a functional ingredient to deal with IBD and related neuronal symptoms. PRACTICAL APPLICATIONS: Prevalence of inflammatory bowel diseases is not uncommon in the modern lifestyle. Gut health is associated with neurological disorders that contribute substantially to the deterioration of quality of life and socioeconomic development. In this research work, the protective action of a black pepper seed extract standardized to 30% ß-caryophyllene (Viphyllin) is evaluated against Dextran sodium sulfate-induced experimental colitis model. Here we have demonstrated the beneficial role of Viphyllin in mitigating intestinal inflammation as a function of NLRP3 inflammasome inhibition. Further, the extract improves intestinal barrier function. In an important aspect of the study, we have provided the data on the effect of Viphyllin on neurological symptoms and brain health in colitis model mice.

Kinetics and computational analysis of cholinesterase inhibition by REVERC3, a bisdemethoxycurcumin-rich Curcuma longa extract: Relevance to the treatment of Alzheimer's disease.

Objectives: Cholinesterase inhibition is a common strategy to treat Alzheimer's disease. In this study, we have investigated the cholinesterase inhibitory effects of a first-of-its-kind turmeric extract (REVERC3) having enriched content of bisdemethoxycurcumin as major active curcuminoid. Methods: The inhibition studies were performed using Ellman's colorimetric assay. The kinetics of acetylcholinesterase and butyrylcholinesterase was determined in the presence of REVERC3 using the Lineweaver-Burk double reciprocal plots. Furthermore, we used AutoDock tools to predict the binding of bisdemethoxycurcumin with the active sites of cholinesterases. Results: REVERC3 showed 4.8- and 5.39-fold higher inhibitory potential of acetylcholinesterase and butyrylcholinesterase with IC50 values of 29.08 and 33.59 µg/mL, respectively, compared to the regular turmeric extract. The mode of binding of REVERC3 was competitive in the case of acetylcholinesterase while it was uncompetitive for the inhibition of butyrylcholinesterase. Docking analysis revealed that bisdemethoxycurcumin, the major constituent of REVERC3, has different preferences of binding in the active sites of acetylcholinesterase and butyrylcholinesterase. However, the best binding pose predictions are in line with the experimental binding mode of the cholinesterases. Conclusion: These results indicate that bisdemethoxycurcumin-enriched turmeric extract could improve the cholinergic functions via dual inhibition of cholinesterases. However, the predominant role of bisdemethoxycurcumin in REVERC3 must be further validated using preclinical studies and clinical trials.