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Cnidium Monnieri

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Background & General Info

Cnidium monnieri, commonly known as Monnier’s snowparsley, is an annual plant native to China but is now vastly distributed in the riparian grasslands, ditches, and field margins of India, Korea, Laos, Mongolia, Vietnam, and Russia. [1] The Chinese refer to its dried fruits as “shechuangzi,” which is regarded as a vital remedy for skin diseases, gynecopathy, and blood stasis. [2]



Botany

Cnidium monnieri is a 10- and 60-meter herb characterized by a thick taproot; striate, scabrous stems; alternately arranged bipinnate leaves; and ovoid fruits. The leaf blades are described as ovate-lanceolate in shape with scabrous veins and margins. The plant’s compound umbels are about 2–3 centimeters across and comprise five stellate flowers that bloom from April to July, whereas its 6–10 bracts are linear to linear-lanceolate in appearance, with narrowly white membranous margins. [1]

History & Traditional Use

As a traditional Chinese medicine, Cnidium monnieri holds an extensive history of use because of its notable range of health benefits and has even been recorded in ancient herbal books and the Pharmacopoeia of the People’s Republic of China. In Chinese medical system, the plant is said to be able to warm the kidney, revitalize the yang, dispel wind and eliminate dampness, and disinfect insects. Its oral ingestion can also externally manage skin diseases and fortify the yang, and its fruits are believed to ease vulvar pain and ulcer, to manage male impotence and epilepsy, and to prolong life when taken over a lengthy period of time. [3]

General Herbal Uses

Cnidium monnieri has long been regarded as a Chinese medicine extensively employed by traditional medicine doctors. [4] This plant, especially its fruits, ranks as one of the most commonly used traditional herbal medicines utilized to treat various conditions and diseases in China, Vietnam, and Japan. [3] According to data from in vitro and in vivo studies, osthole, the most pharmacologically active coumarin in Cnidium monnieri, exerts a broad spectrum of biological activities that are of value in managing disorders of the female genitals, male impotence, frigidity, and skin-related diseases and exhibits strong antipruritic, anti-allergic, antidermatophytic, antibacterial, antifungal, anti-osteoporotic effects. [3]



Constituents/Active Components

Currently, roughly 350 compounds have been isolated and identified from Cnidium monnieri, the primary active constituents being coumarins. [3] Chiou et al. (2001) performed bioassay-directed fractionation on the ethanol extract acquired from the fruits of Cnidium monnieri and identified four known coumarins, namely, osthole, imperatorin, xanthotoxin, and isopimpinellin. [5] Similarly, through bioassay-directed fractionation of Cnidium monnieri ethanol extract, Oh et al. (2002) isolated torilin and torilolone, both of which are sesquiterpenes, as well as a new derivative, 1-hydroxytorilin. [6] Chromone glycosides have also been isolated from the plant, such as monnierisides A–G, as well as other chromone derivatives. [7]

Medicinal/Scientific Research

Cardiovascular

Some studies had validated the protective activity conferred by Cnidium monnieri on the cardiovascular system, such as anti-arrhythmia action, blood vessel expansion, and reduction of blood pressure. [3] Osthole has been confirmed by Zhou et al. (2012) to therapeutically reduce heart hypertrophy in rats by possibly improving myocardial oxidative stress and lipid metabolism. Rats orally treated with 20 mg/kg of osthole for 4 weeks presented lowered blood pressure, heart weight index, and myocardial malondialdehyde content and increased myocardial superoxide dismutase and glutathione peroxidase contents. [8]

The four coumarins identified by Chiou et al. (2001) in Cnidium monnieri ethanol extract (osthole, imperatorin, xanthotoxin, and isopimpinellin) had been found to bring about vasorelaxing effects on the corpus cavernosum (sponge-like tissues of the penis) of experimental rabbits. Their IC50 values were 2.14 ± 0.73, 0.85 ± 0.16, 1.24 ± 0.45, and 18.4 ± 8.10 µM, respectively. [5]

Antioxidant

Findings from a 2014 Taiwanese study indicated that 8-alkylcoumarins isolated from the fruits of Cnidium monnieri protect Neuro-2a neuroblastoma cells against injury and oxidative damage induced by using hydrogen peroxide. The cytoprotective (“cell-protective”) effect of these 8-alkylcoumarins on Neuro-2a cells (neuroblastoma cells) was assayed. The effective cytoprotective dosages of 7-O-methylphellodenol-B, 3′-O-methylvaginol, and 7-methoxy-8-(3-methyl-2,3-epoxy-1-oxobutyl)chromen-2-one were 0.25–1 μM, 0.1 μM, and 0.1 to 1 μM, respectively. [2]

Anticancer

A 2007 study published in the journal Phytotherapy Research investigated osthole, the chief bio-active compound isolated from Cnidium monnieri, and its in vitro and in vivo antitumor effects. Findings from in vitro study indicated time- and concentration-dependent inhibition of the growth of HeLa by Cnidium monnieri’s osthole, with IC50 values of 77.96 and 64.94 µm for 24 and 48 hours, respectively. Furthermore, osthole had been observed to exert lower cytotoxic effects in primary cultured normal cervical fibroblasts and to augment DNA fragmentation and activate PARP in HeLa, inducing apoptosis. Results from the in vivo study on the other hand demonstrated prolonged survival days of the P-388 D1 tumor-bearing CDF(1) mice following 9-day treatment of osthole at a concentration of 30 mg/kg. Overall, osthole has been strongly suggested to inhibit P-388 D1 (macrophage-like tumor) cells in vivo and to induce programmed cell death in HeLa cells in vitro, making this compound an excellent lead for developing antitumor drugs. [4]

Anti-allergy

Study results of Matsuda et al. (2002) suggested the dried fruits of Cnidium monnieri as beneficial remedy to allergic conditions. In particular, 70% ethanol extract from dried Cnidium monnieri fruits demonstrated inhibitory effects on allergic animal models of 48-hour homologous passive cutaneous anaphylaxis; 2, 4-dinitrofluorobenzene-induced contact dermatitis; and picryl chloride-induced contact dermatitis. Such anti-allergic effect of Cnidium monnieri has been associated with its osthole content. [9] Another 2002 study indicated that oral administration of Cnidium monnieri ethanol extract at concentrations of 200 and 500 mg/kg inhibited the scratching behavior of experimental mice. This effect did not have an impact on spontaneous locomotion. [10]

Hepatoprotective

The ethanol extract of Cnidium monnieri contains sesquiterpenes that help protect the liver against injury or damage, namely, torilin and torilolone. Both of these compounds have been found to display hepatoprotective effects on tacrine-induced cytotoxicity in human liver-derived Hep G2 cells, with EC50 values of 20.6 ± 1.86 and 3.6 ± 0.1 µM, respectively. [6]

The therapeutic effect of osthole, the chief active component of Cnidium monnieri fruits, on alcohol-induced fatty liver in mice has also been established by a 2011 study. Experimental mice were fed with 52% alcohol for 4 weeks, resulting in alcoholic fatty liver, and were then treated with osthole at doses of 10, 20, and 40 mg/kg for 6 weeks. Osthole treatment led to a significant decrease in the levels of serum total cholesterol, triglyceride, and low density lipoprotein-cholesterol and to a reduction of liver tissue contents of cholesterol, triglyceride, and malondialdehyde. Compared to the model group, osthole-treated mice had significantly increased level of superoxide dismutase, a powerful antioxidant that repairs cells and limits damage that can be caused by superoxide. Upon evaluation, liver tissues of treated animals were found to manifest dramatically decreased lipid accumulation. Hence, osthole was effective in treating mouse alcoholic fatty liver, which can be attributable to mechanisms that involve reduction of hepatic oxidative stress, such as suppression of production of reactive oxygen species, improvement in antioxidative enzyme activity, and a decrease in lipid accumulation and peroxidation. [11]

Anti-osteoporosis

An early 1997 research by Liao et al. provided convincing evidence on the ability of total coumarins from the dried fruits of Cnidium monnieri to prevent osteoporosis and boost torsional strength of femurs in rats. In rats treated with glucocorticoids to induce osteoporosis, the bone density indices declined for the proximal, middle, and distal segments by 12%, 14%, and 12%, respectively, in comparison to the control group. The bone density indices of the group of rats treated with glucocorticoids and total coumarins from the dried Cnidium monnieri fruits increased by 26%, 34%, and 31% when compared to the rat group treated with glucocorticoids alone. Additionally, rats treated with Cnidium monnieri coumarins were significantly characterized by a 15% improvement in torsional strength, 32% increase in energy, 14% increase in maximal torsional angle, and 13% increase in rigidity. [12]

Meng et al. (2004) on the other hand proposed the potential of Cnidium monnieri extract as an anti-osteoporosis agent because of its constituents that stimulate osteoblasts (or bone-forming cells). In their study, the proliferation-stimulating activity of coumarins from fruits of Cnidium monnieri was evaluated in osteoblast-like UMR106 cells in vitro. Because the chloroform fraction from the crude extract demonstrated the most stimulating activity, its three coumarins (osthole, bergapten, and imperatorin) were tested with regard to their effects on osteoblastic proliferation. However, only osthole significantly stimulated the cells’ activity, with the other two being regarded as less effective. [13]

Anti-obesity

A 2012 Korean study isolated chromone glycosides and their derivatives from the fruits of Cnidium monnieri. What’s interesting is that a few of these compounds were shown to display anti-adipogenic property, or the ability to counter the cell differentiation process by which preadipocytes turn into adipocytes (fat cells). These included cnidimoside A, cnidimoside B, hydroxycnidimoside A, and monnieriside B, which significantly prevented the differentiation of fat cells in 3T3-L1 cells. In the study, fat accumulation was measured using Oil Red O staining. [7]

Contraindications, Interactions, And Safety

Records of Cnidium monnieri in Chinese Pharmacopoeia mention narrow degree of toxicity on the plant’s use. When used to treat asthma, the total coumarins of Cnidium monnieri had been said to produce a slightly bitter mouth, drowsiness, and stomach discomfort as side effects among a small group of patients, although these symptoms disappeared after withdrawal. Nausea and vomiting may also result from Cnidium monnieri use. [3]

References:

[1] "Cnidium monnieri (Linnaeus) Cusson, Mém. Soc. Méd. Emul. Paris. 280. 1782," Flora of China. http://www.efloras.org/florataxon.aspx?flora_id=2&taxon_id=200015495

[2] C. Chi-I, H. Wan-Chiao, S. Che-Piao, H. Ban-Dar, et al., "8-Alkylcoumarins from the fruits of Cnidium monnieri protect against hydrogen peroxide induced oxidative stress damage," International Journal of Molecular Sciences, vol. 15, no. 3, p. 4608–4618, 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975416/

[3] Y. Li, M. Jia, H. Li, N. Zhang, et al., "Cnidium monnieri: a review of traditional uses, phytochemical and ethnopharmacological properties," The American Journal of Chinese Medicine, vol. 43, no. 5, p. 835–877, 2015. https://www.ncbi.nlm.nih.gov/pubmed/26243582

[4] S. Chou, C. Hsu, K. Wang, M. Wang and C. Wang, "Antitumor effects of osthol from Cnidium monnieri: an in vitro and in vivo study," Phytotherapy Research, vol. 21, no. 3, p. 226–230, 2007. https://www.ncbi.nlm.nih.gov/pubmed/17154232

[5] W. Chiou, Y. Huang, C. Chen and C. Chen, "Vasorelaxing effect of coumarins from Cnidium monnieri on rabbit corpus cavernosum," Planta Medica, vol. 67, no. 3, p. 282–284, 2001. https://www.ncbi.nlm.nih.gov/pubmed/11345705

[6] H. Oh, J. Kim, E. Song, et al., "Sesquiterpenes with hepatoprotective activity from Cnidium monnieri on tacrine-induced cytotoxicity in Hep G2 cells," Planta Medica, vol. 68, no. 8, p. 748–749, 2002. https://www.ncbi.nlm.nih.gov/pubmed/12221602

[7] S. Kim, J. Ahn, S. Han, B. Hwang, et al., "Anti-adipogenic chromone glycosides from Cnidium monnieri fruits in 3T3-L1 cells," Bioorganic & Medicinal Chemistry Letters, vol. 22, no. 19, p. 6267–6271, 2012. http://www.sciencedirect.com/science/article/pii/S0960894X12009882

[8] F. Zhou, W. Zhong, J. Xue, Z. Gu and M. Xie, "Reduction of rat cardiac hypertrophy by osthol is related to regulation of cardiac oxidative stress and lipid metabolism," Lipids, vol. 47, no. 10, p. 987–994, 2012. https://www.ncbi.nlm.nih.gov/pubmed/22918576

[9] H. Matsuda, N. Tomohiro, Y. Ido and M. Kubo, "Anti-allergic effects of cnidii monnieri fructus (dried fruits of Cnidium monnieri) and its major component, osthol," Biological and Pharmaceutical Bulletin, vol. 25, no. 6, p. 809–812, 2002. https://www.ncbi.nlm.nih.gov/pubmed/12081154

[10] H. Matsuda, Y. Ido, A. Hirata, et al., "Antipruritic effect of Cnidii Monnieri Fructus (fruits of Cnidium monnieri CUSSON)," Biological and Pharmaceutical Bulletin, vol. 25, no. 2, p. 260–263, 2002. https://www.ncbi.nlm.nih.gov/pubmed/11853179

[11] J. Zhang, J. Xue, H. Wang, Y. Zhang and M. Xie, "Osthole improves alcohol-induced fatty liver in mice by reduction of hepatic oxidative stress," Phytotherapy Research, vol. 25, no. 5, p. 638–643, 2011. https://www.ncbi.nlm.nih.gov/pubmed/20981870

[12] J. Liao, Q. Zhu, H. Lu, et al., "Effects of total coumarins of Cnidium monnieri on bone density and biomechanics of glucocorticoids-induced osteoporosis in rats," Zhongguo Yao Li Xue Bao, vol. 18, no. 6, p. 519–521, 1997. https://www.ncbi.nlm.nih.gov/pubmed/10322909

[13] F. Meng, Z. Xiong, Y. Sun and F. Li, "Coumarins from Cnidium monnieri (L.) and their proliferation stimulating activity on osteoblast-like UMR106 cells," Pharmazie, vol. 59, no. 8, p. 643–645, 2004. https://www.ncbi.nlm.nih.gov/pubmed/15378857

Article researched and created by Dan Albir for herbs-info.com. © herbs-info.com 2018

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