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Codonopsis

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Background & General Info

Codonopsis is a genus of dicotyledonous flowering plants belong to Campanulaceae or the bellflower family. This genus comprises around 42 species of herbaceous perennials that are largely distributed in Central, East, and South Asia and are extensively traditionally employed as herbs with numerous medicinal properties. [1] Some species such as the bonnet bellflower (Codonopsis lanceolata) are exceedingly prized as both an herbal medicine and vegetable. [2] Worthy of mention is Codonopsis pilosula whose dried roots are recognized as cheap substitute with comparable therapeutic effects to the more costly Panax ginseng. [3]



Botany

Codonopsis pilosula is a perennial flowering plant characterized by ovate leaves usually coated with short hairs; glabrous, branched, twining stems; and solitary, bell-shaped flowers at its branching tips. The leaves on the main stems and branches are alternately arranged, whereas those on branchlets are opposite each other. The upper surface of the leaves is green, whereas their lower surface is grayish green. The yellow-green flowers have purple spots inside, and the corolla is broadly campanulate. [4]

Codonopsis lanceolata is a dicotyledonous herbaceous perennial plant with bell-shaped hermaphrodite flowers that are purple inside. Although the entire plant is glabrous, it may be sometimes sparsely villous on its stems and leaves, and its twining stems are yellowish green but with purplish shade and are often branched. The lanceolate, ovate, or elliptic leaves are alternately arranged on the main stems. Flowers emerge singly or as a pair atop the branchlets, with broadly campanulate corolla having shallow yellow-green or milky white lobes with purple spots. [5]

History & Traditional Use

For centuries, the fresh or dried roots of Codonopsis pilosula, Codonopsis pilosula var. modesta, Codonopsis tangshen, and Codonopsis lanceolata have been traditionally used in folk medicine and are collectively considered as herbal medicines. [1] According to the 2010 edition of the Chinese Pharmacopoeia, Radix Codonopsis consists of the dried roots of Codonopsis pilosula, Codonopsis pilosula var. modesta, and Codonopsis tangshen and is excellent in replenishing qi (vital energy), boosting the immune system, improving poor gastrointestinal function and appetite, and decreasing blood pressure. [6] Often referred to as “dang-shen” in Chinese, the Radix Codonopsis stands as one of the most recognized traditional Chinese medicines used mainly as a tonic. [7]

In traditional Chinese medicine, Codonopsis lanceolata is a highly valued herb whose roots are commonly consumed as a vegetable in few Asian countries. [2] Folk medicinal systems in Korea, Japan, and China prescribe Codonopsis lanceolata as a centuries-old remedy for lung inflammatory diseases. [8]

General Herbal Uses

Because of its medicinal properties, Codonopsis lanceolata is widely employed as treatment of edema, tuberculosis, bronchitis, asthma, cough, spasms, psychoneurosis, cancer, dyspepsia, colitis, obesity, hyperlipidemia, hepatitis, and lung injury. [9][10] Its rhizomes are also considered herbal medicines for inflammation, insomnia, and hypomnesia. [11] Moreover, several studies had confirmed its antidiabetic, anticancer, antiobesity, antilipogenic, and hepatoprotective effects. [12]



Constituents/Active Components

A number of phytochemical studies identified polyacetylenes, phenylpropanoids, alkaloids, triterpenoids, and polysaccharides in different Codonopsis species. [1] For instance, Codonopsis lanceolata has been found to contain a number of biologically active constituents, including polyphenols, saponins, tannins, triterpene, alkaloids, and steroids. [10] Ichikawa et al. (2009) determined seven triterpenoid saponins from the roots of Codonopsis lanceolata, namely, lancemaside A, lancemaside B, lancemaside C, lancemaside E, lancemaside G, foetidissimoside A, and aster saponin Hb. The most abundant saponin, lancemaside A, was within a concentration range of 2.65 to 3.64 mg/g in the dry root samples. [9] On the other hand, Qi et al. (2011) isolated 12 compounds from Codonopsis pilosula through column chromatography, namely, hesperidin, n-hexyl beta-sophoroside, atractylenolide III, lobetyolin, lobetyolinin, taraxerol, taraxeryl acetate, alpha-spinasterol, 9,10,13-trihydroxy-(E)-11-octadecenoic acid, beta-sitosterol, and beta-daucosterol. [13] According to Lin, Tsai, and Kuo (2013), who utilized a technique combining solvent partition and HPLC-UV to chemically distinguish Codonopsis samples, codonopyrrolidums A and B and codonoside A only exist in Codonopsis tangshen, but not in Codonopsis pilosula var. modesta and Codonopsis pilosula. [7]

Medicinal/Scientific Research

Antioxidant

A 2004 study investigated the antioxidant effects of aqueous and organic extracts from Codonopsis pilosula and four other herbs and determined the aqueous extract of Codonopsis pilosula to be the most potent as regards inhibition of erythrocyte hemolysis. Its organic extract however had weaker potency in inhibiting lipid peroxidation. [3]

Anticancer

Yang et al. (2013) isolated and structurally characterized the pectic polysaccharide CPP1b from Codonopsis pilosula. This carbohydrate is pharmacologically important since it had been shown to display dose- and time-dependent antitumor activity and cytotoxicity against human lung adenocarcinoma A549 cells. [14] A polysaccharide fraction from Codonopsis lanceolata had also been confirmed to exhibit inhibitory activity against melanoma cells and to prevent their metastasis in vivo. Evaluation using Transwell assay also indicated that this fraction caused impairment of β1 integrin-mediated migration of B16F10 melanoma cells in vitro. [15]

Anti-inflammatory

Codonolasides I–III, which are triterpenoid saponins isolated from Codonopsis lanceolata roots, had been revealed to display anti-inflammatory property, as shown in inhibitory effect assay wherein mouse ear edema had been induced by xylene. [16] Lancemaside A, another component of Codonopsis lanceolata, exerts anti-inflammatory function through its strong antioxidative and nuclear factor-κB (NF-κB)-inhibitory activities. In the study of Kim et al. (2014), this compound considerably curbed the inflammatory functions of lipopolysaccharide-treated macrophages (RAW264.7 cells) via inhibition of nitric oxide production, upregulation of the costimulatory molecule CD80, expression of inducible NO synthase (iNOS), and morphological changes elicited by exposure to lipopolysaccharide. [12]

Antidiabetic

A 2011 research on the antidiabetic efficacy of various traditional Chinese medicines in streptozotocin-diabetic mice determined Codonopsis pilosula as one of the 13 herbs out of the 34 tested plants to significantly reduce plasma glucose levels and hinder any elevation of serum aldose reductase activity. Such effect can possibly beneficially delay the development of diabetes and its complications. [17]

Antiobesity

Codonopsis lanceolata can also serve as a functional food with antiobesity benefits. Choi et al. (2013) demonstrated that oral feeding of Codonopsis lanceolata to Sprague-Dawley obese rats lowered body weight gains and significantly reduced weight of adipose pads and serum levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Based on measurement results from Oil Red O staining and reverse transcription-polymerase chain reaction, 3T3-L1 cells treated with wild Codonopsis lanceolata were characterized by suppressed accumulation of lipids and expression of C/EBPα and PPARγ. [18]

Immunity Enhancing

Preliminary immunological tests performed by Yongxu and Jicheng (2008) in vitro indicated that the water-soluble polysaccharide isolated from Codonopsis pilosula roots could dose-dependently stimulate lymphocyte proliferation induced by concanavalin A or lipopolysaccharide. [19] Results from a 2007 study demonstrated the regulatory effects of total methanol extracts obtained from fresh leaves and roots of Codonopsis lanceolata on immune responses mediated by macrophages. These extracts were found to significantly hinder the production of pro-inflammatory mediators such as nitric oxide and tumor necrosis factor-alpha (TNF-α) without changing mRNA levels and to intensely lessen the expression of interleukin-3 (IL-3) and interleukin-6 (IL-6). Additionally, 6 hours of exposure to the extracts led to the blockade of the Raf-ERK signaling pathway. [8]

Hepatoprotective

Dietary supplementation with water extract from Codonopsis lanceolata roots, as indicated by the findings of Cho et al. (2009), displays a protective effect against alcoholic fatty liver and offsets its development in rats. Feeding of ethanol diet supplemented with 0.5% Codonopsis lanceolata root extract for 8 weeks resulted in ameliorated accumulations of cholesterol and triglycerides in the livers of rat models of chronic alcohol consumption and in a reversal of ethanol-induced upregulations of TNF-α, LXR-α, SREBP-1c, HMGR, and LDLR genes in the liver. [20]

Learning And Memory

Findings from Singh et al.’s (2004) study demonstrated the ability of herbal combination of Codonopsis pilosula and Gingko biloba to improve memory acquisition and retention in healthy human subjects and to enhance cognitive function and overall health status. This double-blind, randomized, placebo-controlled trial involved 60 subjects aged 21–60 years who either took a combination capsule comprising 75 mg of Codonopsis pilosula total glycosides and 40 mg of Gingko biloba extract, Gingko biloba extract alone, or placebo. Compared to placebo, the combination product brought forth enhancement in acquisition and retention. [21]

Oral administration of lancemaside A and echinocystic acid, its metabolite, had been confirmed to improve memory and learning deficits in mice through potent dose-dependent inhibition of acetylcholinesterase activity and induction of the expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding protein (p-CREB). In the passive avoidance, Y-maze, and Morris water maze tasks, both compounds considerably reversed the memory and learning deficits induced by scopolamine, although the reversion caused by echinocystic acid was more potent than that of lancemaside A. [11]

Chronic Obstructive Pulmonary Disease (COPD)

A systematic review and meta-analysis on the effectiveness of Codonopsis pilosula as treatment of chronic obstructive pulmonary disease (COPD) had been carried out by Shergis et al. (2015). The 48 randomized controlled trials included in the review showed that Codonopsis pilosula can improve the forced expiratory volume in the lungs and quality of life in comparison to conventional pharmacotherapy and can decrease the frequency of COPD exacerbations. [22]

Contraindications, Interactions, And Safety

To date, there exist no reports on the toxicity of Codonopsis plants in the scientific literature. [1] A 2015 systematic review and meta-analysis amassed data regarding the few reported adverse events related to the use of Codonopsis pilosula as COPD treatment, including gastrointestinal upset, dry mouth, and insomnia. [22]

References:

[1] J.-Y. He, N. Ma, S. Zhu, et al., "The genus Codonopsis (Campanulaceae): a review of phytochemistry, bioactivity and quality control," Journal of Natural Medicines, vol. 69, p. 1–21, 2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287686/

[2] W. Guo, L. Gong, Z. Ding, et al., "Genomic instability in phenotypically normal regenerants of medicinal plant Codonopsis lanceolata Benth. et Hook. f., as revealed by ISSR and RAPD markers," Plant Cell Reports, vol. 25, no. 9, p. 896–906, 2006. https://www.ncbi.nlm.nih.gov/pubmed/16575572

[3] T. Ng, F. Liu and H. Wang, "The antioxidant effects of aqueous and organic extracts of Panax quinquefolium, Panax notoginseng, Codonopsis pilosula, Pseudostellaria heterophylla and Glehnia littoralis," Journal of Ethnopharmacology, vol. 93, no. 2–3, p. 285–288, 2004. https://www.ncbi.nlm.nih.gov/pubmed/15234766

[4] "Codonopsis pilosula (Franchet) Nannfeldt," Flora of China. http://www.efloras.org/florataxon.aspx?flora_id=2&taxon_id=200022921

[5] "Codonopsis lanceolata (Siebold & Zuccarini) Trautvetter," Flora of China. http://www.efloras.org/florataxon.aspx?flora_id=2&taxon_id=200022912

[6] Chinese Pharmacopoeia Commission. Pharmacopoeia of the People’s Republic of China, Beijing: China Medical Science Press, 2010.

[7] L. Lin, T. Tsai and C. Kuo, "Chemical constituents comparison of Codonopsis tangshen, Codonopsis pilosula var. modesta and Codonopsis pilosula," Natural Product Research, vol. 27, no. 19, p. 1812–1815, 2013. https://www.ncbi.nlm.nih.gov/pubmed/23506253

[8] Y. Lee, J. Kim, J. Lee, et al., "Regulatory effects of Codonopsis lanceolata on macrophage-mediated immune responses," Journal of Ethnopharmacology, vol. 112, no. 1, p. 180–188, 2007. https://www.ncbi.nlm.nih.gov/pubmed/17418512

[9] M. Ichikawa, S. Ohta, et al., "Simultaneous determination of seven saponins in the roots of Codonopsis lanceolata by liquid chromatography-mass spectrometry," Journal of Natural Medicines, vol. 63, no. 1, p. 52–57, 2009. https://www.ncbi.nlm.nih.gov/pubmed/18841442

[10] M. Hossen, M. Kim, J. Kim and J. Cho, "Codonopsis lanceolata: a review of its therapeutic potentials," Phytotherapy Research, vol. 30, no. 3, p. 347–356, 2016. https://www.ncbi.nlm.nih.gov/pubmed/26931614

[11] I. Jung, et al., "Lancemaside A isolated from Codonopsis lanceolata and its metabolite echinocystic acid ameliorate scopolamine-induced memory and learning deficits in mice," Phytomedicine, vol. 20, no. 1, p. 84–88, 2012. https://www.ncbi.nlm.nih.gov/pubmed/23079229

[12] E. Kim, W. S. Yang, J. H. Kim, et al., "Lancemaside A from Codonopsis lanceolata modulates the inflammatory responses mediated by monocytes and macrophages," Mediators of Inflammation, vol. 2014, p. 405158, 2014. https://www.hindawi.com/journals/mi/2014/405158/

[13] H. Qi, R. Wang, Y. Liu and Y. Shi, "Studies on the chemical constituents of Codonopsis pilosula," Zhong Yao Cai, vol. 34, no. 4, p. 546–548, 2011. https://www.ncbi.nlm.nih.gov/pubmed/21809539

[14] C. Yang, Y. Gou, J. Chen, et al., "Structural characterization and antitumor activity of a pectic polysaccharide from Codonopsis pilosula," Carbohydrate Polymers, vol. 98, no. 1, p. 886–895, 2013. https://www.ncbi.nlm.nih.gov/pubmed/23987425

[15] Y. Liu, X. Zou, G. Sun and Y. Bao, "Codonopsis lanceolata polysaccharide CLPS inhibits melanoma metastasis via regulating integrin signaling," International Journal of Biological Macromolecules, vol. 103, p. 435–440, 2017. https://www.ncbi.nlm.nih.gov/pubmed/28527988

[16] L. Xu, H. Wang and Z. Yuan, "Triterpenoid saponins with anti-inflammatory activity from Codonopsis lanceolata," Planta Medica, vol. 74, no. 11, p. 1412–1415, 2008. https://www.ncbi.nlm.nih.gov/pubmed/18666043

[17] K. He, X. Li, X. Chen, et al., "Evaluation of antidiabetic potential of selected traditional Chinese medicines in STZ-induced diabetic mice," Journal of Ethnopharmacology, vol. 137, no. 3, p. 1135–1142, 2011. https://www.ncbi.nlm.nih.gov/pubmed/21798327

[18] H. Choi, E. Won, Y. Jang and S. Choung, "Antiobesity effect of Codonopsis lanceolata in high-calorie/high-fat-diet-induced obese rats," Evidence-Based Complementary and Alternative Medicine, vol. 2013, p. 210297, 2013. https://www.hindawi.com/journals/ecam/2013/210297/

[19] S. Yongxu and L. Jicheng, "Structural characterization of a water-soluble polysaccharide from the Roots of Codonopsis pilosula and its immunity activity," International Journal of Biological Macromolecules, vol. 43, no. 3, p. 279–282, 2008. https://www.ncbi.nlm.nih.gov/pubmed/18640151

[20] K. Cho, S. Kim, S. Park, S. Kim and T. Park, "Protective effect of Codonopsis lanceolata root extract against alcoholic fatty liver in the rat," Journal of Medicinal Food, vol. 12, no. 6, p. 1293–1301, 2009. https://www.ncbi.nlm.nih.gov/pubmed/20041784

[21] B. Singh, H. Song, X. Liu, et al., "Dangshen (Codonopsis pilosula) and Bai guo (Gingko biloba) enhance learning and memory," Alternative Therapies In Health And Medicine, vol. 10, no. 4, p. 52–56, 2004. https://www.ncbi.nlm.nih.gov/pubmed/15285274

[22] J. Shergis, S. Liu, X. Chen, A. Zhang, et al., "Dang shen [Codonopsis pilosula (Franch.) Nannf] herbal formulae for chronic obstructive pulmonary disease: a systematic review and meta-analysis," Phytotherapy Research, vol. 29, no. 2, p. 167–186, 2015. https://www.ncbi.nlm.nih.gov/pubmed/25336444

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

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