Cimicifuga racemosa Extract Ze 450 Re-Balances Energy Metabolism and Promotes Longevity

Recently, we reported that the Cimicifuga racemosa extract Ze 450 mediated protection from oxidative cell damage through a metabolic shift from oxidative phosphorylation to glycolysis. Here, we investigated the molecular mechanisms underlying the effects of Ze 450 against ferroptosis in neuronal cells, with a particular focus on mitochondria. The effects of Ze 450 on respiratory complex activity and hallmarks of ferroptosis were studied in isolated mitochondria and in cultured neuronal cells, respectively. In addition, Caenorhabditis elegans served as a model organism to study mitochondrial damage and longevity in vivo. We found that Ze 450 directly inhibited complex I activity in mitochondria and enhanced the metabolic shift towards glycolysis via cMyc and HIF1α regulation. The protective effects against ferroptosis were mediated independently of estrogen receptor activation and were distinct from effects exerted by metformin. In vivo, Ze 450 protected C. elegans from the mitochondrial toxin paraquat and promoted longevity in a dose-dependent manner. In conclusion, Ze 450 mediated a metabolic shift to glycolysis via direct effects on mitochondria and altered cell signaling, thereby promoting sustained cellular resilience to oxidative stress in vitro and in vivo.

Herb-Induced Liver Injury by Cimicifuga racemosa and Thuja occidentalis Herbal Medications for Fertility

Herb-induced liver injury (HILI) is often an underreported sequela for many herbal remedies due to the lack of safety measurements involving these supplements. Cimicifuga racemosa and Thuja occidentalis are two herbal medications commonly used by women for fertility purposes. Many herbal preparations of these two supplements do not specify the risks behind their individual usage. We present a case of a 40-year-old woman who developed acute liver injury after concomitant use of these two products assessed for causality using the updated RUCAM. Upon a detailed investigation, the patient did not have evidence of underlying liver disease or any other risk factors to explain her presentation. After discontinuation of both herbal supplements, the patient had complete resolution of her symptoms and a significant improvement of transaminitis. This report highlights the importance of potential risk of hepatotoxicity induced by concomitant use of Cimicifuga racemosa and Thuja occidentalis.

Black cohosh associated mania in a patient with unipolar depression

Black cohosh ( actaea racemosa, cimicifuga racemosa) a popular complementary medicine, is commonly prescribed as an alternative drug to hormone replacement therapy for the treatment of menopause symptoms and menstrual pain. Studies on the black cohosh’s psychological effects are generally focused on the perimenopausal depression and anxiety; and, its effects have been considered to be affiliated with its serotonergic and dopaminergic activities. We report a patient presenting with acute onset mania associated with black cohosh use, probably due to its psychopharmacological activities on serotonergic and dopaminergic receptors. We suggest that black cohosh must be used cautiously in the patients with history of unipolar depression or bipolar disorder.