Sheng Ma

The most complete review of Sheng Ma as the Chinese Pharmacopoeia defines it - the dried rhizome of Cimicifuga foetida, C. dahurica and C. heracleifolia, explicitly not Actaea racemosa. It catalogues 348 compounds (211 triterpenoid saponins, 67 phenylpropanoids, 10 chromones, 7 alkaloids), records isoferulic acid as the sole Pharmacopoeia marker at not less than 0.10 percent and argues for a multi-marker standard. Its clinical section is short and revealing: a Cimicifuga triterpenoid saponin tablet that improved menopausal symptoms without changing hormone levels or endometrial thickness, C. foetida with adefovir in 60 chronic hepatitis B patients, C. foetida for menopausal breast pain in 96 women, and multi-herb Sheng Ma decoctions for herpes zoster, oral ulcers and lupus. These are small, largely Chinese-language, and mostly not blinded. Its toxicity section attaches hepatic findings to C. dahurica and C. heracleifolia, not to C. foetida, and notes that the human adverse-reaction reports concern black cohosh.

Motivated by the finding that market black cohosh was adulterated with Asian Cimicifuga whose fibrous roots had not been removed, this study separated rhizome from fibrous root in Cimicifuga dahurica, extracted both with 70 percent ethanol and identified 39 compounds (chiefly saponins and phenolic acids). Fibrous root extract was more cytotoxic to L-02 hepatocytes than rhizome (IC50 1.26 versus 1.417 mg/mL), and in a 90-day sub-chronic study it significantly raised white cells, ALP, ALT, AST, bilirubin and cholesterol, caused extensive granular and ballooning degeneration in liver tissue, and raised nuclear p-NF-kappaB dose-dependently. The species is C. dahurica, one of the three official Sheng Ma species but not C. foetida, and the finding is about a plant part the Pharmacopoeia already says to remove.

Combined mouse excretion study, human liver microsome incubation and analytical survey of 128 Kampo extract products by lateral flow immunoassay, ELISA and LC-MS/MS. Coclaurine administration produced urinary higenamine in mice and higenamine formation in human liver microsomes. Cimicifuga rhizome was newly confirmed to contain higenamine, and also newly identified as containing coclaurine - one of only six and nine crude drugs respectively in that position. Higenamine has been WADA-prohibited since 2017. The study quantifies the drugs, not the urinary levels a therapeutic human dose would produce, so it establishes the hazard without sizing the risk.

Pseudoparticle-based screen of heat-clearing herbs and formulas for SARS-CoV-2 entry inhibition. The water extract of Cimicifuga foetida rhizome - the species this monograph describes, and prepared the way the drug is actually decocted - was the most potent of those tested, and caffeic acid was identified as the active component, blocking entry of both wild-type and JN.1 pseudoparticles and inactivating the particles directly. Sheng Ma Ge Gen Tang, the classical formula built on this herb, was also active. This is cell-culture work with pseudoparticles, not live virus and not patients.

A purified Cimicifuga foetida polysaccharide (SM05, composed of mannose, glucose, galactose and arabinose) reduced disease activity index, colon shortening and histological injury in dextran sodium sulfate colitis in mice, activating Nrf2/Keap1, suppressing NLRP3-dependent pyroptosis, preserving tight junction proteins and shifting the microbiota away from Bacteroides and Desulfovibrio towards Akkermansia. Species-specific to C. foetida and uses the water-extractable fraction, but it is a purified single fraction in a chemical colitis model, not the crude drug in patients.

Affinity-ultrafiltration mass spectrometry with molecular docking, enzyme kinetics and network pharmacology identified cimifugin, cimifugoside, caffeic acid, ferulic acid and isoferulic acid from Cimicifuga foetida as acetylcholinesterase active-site binders. Useful as a chemical map of the species, but binding affinity in a screening assay is a long way from an anti-Alzheimer effect, and the authors do not claim otherwise.

Included here as the contrast, not as evidence about Sheng Ma. Sixteen randomised trials in 2,027 perimenopausal and postmenopausal women, all using oral monopreparations of black cohosh at a median 40 mg daily for a mean 23 weeks, compared with placebo, hormone therapy, red clover or fluoxetine. There was no significant difference from placebo in hot flush frequency. Every trial used Cimicifuga racemosa (Actaea racemosa), the North American species, which is NOT one of the three species the Chinese Pharmacopoeia recognises as Sheng Ma. Nearly the entire menopause and hepatotoxicity literature for the genus sits here, and none of it transfers to Cimicifuga foetida.