Rhizoma Coptidis and Berberine as a Natural Drug to Combat Aging and Aging-Related Diseases via Anti-Oxidation and AMPK Activation

Abstract

Aging is the greatest risk factor for human diseases, as it results in cellular growth arrest, impaired tissue function and metabolism, ultimately impacting life span. Two different mechanisms are thought to be primary causes of aging. One is cumulative DNA damage induced by a perpetuating cycle of oxidative stress; the other is nutrient-sensing adenosine monophosphate-activated protein kinase (AMPK) and rapamycin (mTOR)/ ribosomal protein S6 (rpS6) pathways. As the main bioactive component of natural Chinese medicine rhizoma coptidis (RC), berberine has recently been reported to expand life span in Drosophila melanogaster, and attenuate premature cellular senescence. Most components of RC including berberine, coptisine, palmatine, and jatrorrhizine have been found to have beneficial effects on hyperlipidemia, hyperglycemia and hypertension aging-related diseases. The mechanism of these effects involves multiple cellular kinase and signaling pathways, including anti-oxidation, activation of AMPK signaling and its downstream targets, including mTOR/rpS6, Sirtuin1/ forkhead box transcription factor O3 (FOXO3), nuclear factor erythroid-2 related factor-2 (Nrf2), nicotinamide adenine dinucleotide (NAD+) and nuclear factor-κB (NF-κB) pathways. Most of these mechanisms converge on AMPK regulation on mitochondrial oxidative stress. Therefore, such evidence supports the possibility that rhizoma coptidis, in particular berberine, is a promising anti-aging natural product, and has pharmaceutical potential in combating aging-related diseases via anti-oxidation and AMPK cellular kinase activation.

Antimalarial activity of traditional Kampo medicine Coptis Rhizome extract and its major active compounds

“…After the oral administration of Coptis Rhizome and Orengedokuto, coptisine were detected in 1/5 and 3/5 of mice, respectively, and the signal of coptisine in plasma samples were relatively lower than that of berberine. The content of coptisine is approximately 1/16 of coptisine in Coptis Rhizome [54]. Therefore, our results re ect the contents of these alkaloids in Coptis Rhizome which suggest that the poor oral absorption and bioavailability, and fast elimination rate of coptisine [38,39].…”

Metabolic profile of alkaloids in Rhizoma Coptidis in rat plasma, urine and feces after oral administration using ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry

“…In the MS/MS spectra, product ions at m/z 297.1119 [M − CH 4 − NHCH 2 ] + , 282.0883 [M − C 2 H 7 N − CH 3 ] + , 265.0855 [M − CH 4 − NHCH 2 − CH 3 − OH] + and 237.0899 [M − CH 4 − NHCH 2 − CH 3 − OH − CO] + were observed. By comparison with literature data, P7 was identified as magnoflorine. P8 was eluted at t R = 7.57 min and had a [M] + ion at m/z 322.1073 (C 19 H 16 NO 4 ), yielding product ions at m/z 307.0835 [M − CH 3 ] + , 294.1102 [M − CO] + , 279.0889 [M − CH 3 − CO] + and 251.0921 [M − CO] + .…”

“…RC, first mentioned in Shennong's Classic of Materia Medica in the Eastern Han Dynasty, has been used to treat various diseases in traditional Chinese medicine (TCM) for thousands of years . Previous studies have demonstrated that RC has activities including anti‐hyperglycemic, anti‐cancer, anti‐bacterial, anti‐hyperlipidemic, anti‐inflammatory, anti‐obesity and anti‐hepatic steatosis . Currently, more than 120 components have been isolated and identified from RC, and alkaloids are most common in plants from RC .…”

“…Previous studies have demonstrated that RC has activities including anti‐hyperglycemic, anti‐cancer, anti‐bacterial, anti‐hyperlipidemic, anti‐inflammatory, anti‐obesity and anti‐hepatic steatosis . Currently, more than 120 components have been isolated and identified from RC, and alkaloids are most common in plants from RC . Protoberberine alkaloids, including berberine, jatrorrhizine, palmatine, coptisine, etc., are the main components of RC that play a pharmacological role.…”

Establishing a Comprehensive Anti-aging Research Center: Experiences and Challenges

“…The most immediate result of aging is an increase in the incidence of age-related diseases 1 . It is well known that chronic non-communicable diseases have been the major contributors to the disease burden, among which age-related diseases such as diabetes, cardiovascular disease, and cancer diseases have become the leading causes of morbidity and mortality worldwide [2][3][4][5][6][7][8][9] . Moreover, these diseases could not only affect the life quality of the elderly, but also the family members who take care them 10 .…”