Berberine and its derivatives as candidate modulators of immunosenescence: a critical evaluation.

Berberine has been widely used in traditional and folk medicine for many years. The molecular mechanisms of berberine's action are pleiotropic and have been fairly well studied. Its applications are generally limited to cardiometabolic diseases and cancer therapy, and a focused critical evaluation of berberine and its derivatives in the specific context of immunosenescence remains limited. Immunosenescence represents an age-associated remodeling of the innate and adaptive immune systems, closely linked to impaired immunometabolism, chronic inflammation, and shifts in the AMPK/mTOR, NF-κB, autophagy, and inflammasome pathways; therefore, berberine is a logical candidate for the role of a multi-target regulator of these processes. In this review, we examine the molecular mechanisms of immunosenescence and their biomarkers, and critically evaluate the effects of berberine on these parameters. Here we provide a detailed examination of the rationale for using berberine as a modulator of immunosenescence and proposes a design for future studies.