Working with the natural complexity: Selection and characterization of black cohosh root extract for use in toxicology testing

A cross‐sectional clinical study in women to investigate possible genotoxicity and hematological abnormalities related to the use of black cohosh botanical dietary supplements

“…Approximately 94% of the constituents of black cohosh remain unidentified and the compounds responsible for the observed genotoxicity in the DNTP studies have not been identified. Detailed characterization of the composition of the NTP BCE using targeted and non‐targeted chemical analysis confirmed the suitability of the sample (authentic, non‐adulterated, close resemblance to the popular product Remifemin) for use in pre‐clinical studies (Waidyanatha et al, 2022). Furthermore, findings from the DNTP fractionation studies, aimed at identifying the specific genotoxic constituents(s) of BC extract, may support refined ADME studies for BC extract in humans and allow a more accurate interpretation of health hazard, if any, associated with the recommended doses of BC products.…”

“…The limitation posed by the diversity of products used by participants in this study derives from a basic challenge in studying the toxicological effects of botanical materials: chemical composition of the preparations can vary considerably due to, e.g., differences in growing conditions, parts of the plant extracted, solvents used for extraction, manufacturing processes, and adulteration (Ryan et al, 2019; Shipkowski et al, 2018; Waidyanatha et al, 2022). Variable composition can lead to variable biological activity.…”

“…Black cohosh is available in a variety of forms, including as an extract, root powder, tincture, or oral spray, and in combination with other botanicals. Black cohosh extract is made from the root of the plant, and over 100 constituents have been identified among various preparations (Nikolić et al, 2015; Qiu et al, 2014; Waidyanatha et al, 2022; Wang et al, 2011). Long used by Native Americans for a variety of medicinal purposes, BC was recorded in the first edition of the United States Pharmacopeia in 1820 (Mahady et al, 2008).…”

“…In response to the nomination of BC, the DNTP initially conducted standard 90-day toxicity studies in female Wistar Han rats and B6C3F1/N mice using a BC extract bearing a chromatographic profile similar to Remifemin ® Menopause Tablets, a popular, standardized, BC product (Waidyanatha et al, 2022). Results showed that BC extract, administered by gavage at doses ranging up to 1000 mg/kg/ day, was not hepatotoxic and did not modulate estrogenic signaling (Mercado-Feliciano et al, 2012).…”

“…Several standard hematological and clinical chemistry parameters with well-characterized methods of analysis were also evaluated in the study participants. In addition, chemical profiles of the supplements used by participants were generated to allow comparisons in chemical composition among the different products and to compare each of the products to the DNTP BC extract (Waidyanatha et al, 2022) that induced MN in the rodent studies (Mercado-Feliciano et al, 2012).…”