Pharmacological Effects and Clinical Applications of Codonopsis Radix

Codonopsis Radix is the dried root of Campanulaceae plants, including Codonopsis pilosula, Codonopsis pilosula var. modesta, and Codonopsis tangshen, and is a commonly used traditional Chinese medicine for nourishing and replenishing. It has the effects of invigorating the spleen and lungs, nourishing blood, and promoting the production of body fluids. The phytochemical composition of Codonopsis Radix is complex. So far, scholars at home and abroad have isolated and identified over 230 compounds from the genus Codonopsis, including alkaloids, alkynes, terpenes, flavonoids, lignans, sterols, and polysaccharides. Among them, alkaloids, polyalkynes, lignans, flavonoids, and polysaccharides are considered the main active ingredients. Codonopsis Radix exhibits a wide range of pharmacological effects, primarily acting on the nervous system, endocrine system, and immune system. Numerous studies have found that Codonopsis Radix has neuroprotective, antitumor, antioxidant, anti-inflammatory, anti-stress, and liver-protecting effects.

1. Protection of the Nervous System

Codonopsis Radix extracts possess neuroprotective effects, including protecting nerve cells, enhancing learning and memory abilities, and alleviating symptoms of Alzheimer's Disease (AD). The aqueous extract of Codonopsis Radix and its monomeric component Lancemaside A can upregulate the activity of Protein Phosphatase 2A (PP2A), reduce the phosphorylation level of Tau protein, repair damaged neurons, and inhibit AChE activity. The total alkaloids of Codonopsis Radix can enhance neurite outgrowth in PC12 cells and increase the phosphorylation of Mitogen-Activated Protein Kinases. Additionally, the total saponins of Codonopsis Radix can improve the survival rate of astrocytes in rats after cerebral ischemia-reperfusion injury. Further research indicates that the polysaccharides of Codonopsis Radix primarily prevent the excessive phosphorylation of AD-like Tau protein by activating PP2A.

2.Regulation of Blood Glucose and Blood Lipids

Codonopsis Radix extracts exhibit effects on regulating blood glucose and blood lipids. The aqueous extract of Codonopsis Radix can lower blood glucose levels, inhibit aldose reductase activity, and delay the progression of diabetes. The total saponins of Codonopsis Radix can reduce serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels in hyperlipidemic rats while increasing NO and high-density lipoprotein cholesterol levels, demonstrating its blood lipid-regulating effect. The polysaccharide CLPS of Codonopsis Radix alleviates insulin resistance induced by a high-fat/high-sugar diet through antioxidative stress. Neutral polysaccharides from Codonopsis Radix significantly improve insulin secretion in INS-1 cells and lower blood glucose concentrations in type 2 diabetic mice.

3.Effects on the Immune System

Codonopsis Radix possesses the ability to regulate the immune balance of the body. The methanol extract of Codonopsis Radix can modulate macrophage-mediated immune responses and promote anti-inflammatory activity. Luludangshen Oral Liquid improves the immune function of mice with immunosuppression induced by cyclophosphamide. Furthermore, when the total saponins of Codonopsis Radix are formulated into nanoemulsions, their regulatory functions on cellular immunity, humoral immunity, and non-specific immunity are enhanced. As a natural immunomodulator, the polysaccharides of Codonopsis Radix maintain the balance of T-cells in mice. By regulating T-cell circulation, the polysaccharides of Codonopsis Radix can attenuate sepsis induced by cecal ligation and puncture in mice. They also promote phagocytosis by alveolar macrophages damaged by chronic obstructive pulmonary disease, improving the inflammatory response. Selenized polysaccharides of Codonopsis Radix can improve the phagocytic index of peritoneal macrophages and induce the secretion of TNF-α and IL-6. The endogenous extracellular polysaccharides of Codonopsis Radix activate macrophages and inhibit cancer cell proliferation and migration. Additionally, two pectic polysaccharides, RCAP-1 and RCAP-2, from Codonopsis Radix also exhibit significant immunomodulatory effects.

4.Effects on the Digestive System

Extracts of Codonopsis Radix exhibit pharmacological effects such as treating gastric ulcers, promoting intestinal motility, and enhancing the body's digestive capabilities. After administering a decoction of Codonopsis Radix to Japanese big-eared white rabbits, the concentration of somatostatin in the gastric antrum and duodenal mucosa significantly increased, indicating its potential in treating peptic ulcers. The aqueous extract of Codonopsis Radix can promote defecation in mice with constipation. Ultra-fine powder of Codonopsis Radix protects the gastric mucosa of rats with gastric ulcers. The flavonoid-rich fraction of Codonopsis Radix promotes the migration of small intestinal epithelial cells, reverses the inhibition of cell migration caused by DFMO or 4-AP, and increases intracellular arginine content, possibly through modulation of the polyamine signaling pathway. Codonopsisine, a compound in Codonopsis Radix, elevates prostaglandin (PG) levels, counteracts the acid-secreting effect of gastrin (Gas), stimulates the synthesis and release of epidermal growth factor in the gastric mucosa, and provides a certain degree of protection against ethanol-induced gastric mucosal injury. Polysaccharides from Codonopsis Radix increase the thickness of the gastric mucosa and gastric wall, promote the growth of intestinal villi, enhance intestinal motility, improve digestive function, and regulate gut microbiota in mice with colitis. The inulin-type fructan in Codonopsis Radix can improve gastrointestinal function by altering the composition and metabolism of intestinal microbiota, making it a potential prebiotic and a promising component for treating acute gastric ulcers.

5.Effects on Blood Circulation

Extracts of Codonopsis Radix exhibit various effects on blood circulation, including treating heart failure, regulating blood cell growth and development, enhancing hematopoietic function, and inhibiting platelet aggregation. Codonopsis Radix can alleviate damage to the insulin-like growth factor II receptor pathway in myocardial cells, thereby reducing myocardial cell apoptosis. The aqueous solution of Codonopsis Radix can lower left ventricular end-diastolic pressure, inhibit the elevation of MDA, LDH, and CK, and enhance the activities of SOD, GSH-Px, Na+-K+-ATP, and Ca2+-ATP, providing protection against myocardial ischemia/reperfusion injury. Furthermore, Codonopsis Radix extracts can increase the maximum rates of left ventricular pressure rise and fall, improve symptoms in rats with chronic heart failure, and delay the onset and progression of the disease. Codonopsis Radix granules can also treat heart failure in mice by elevating ejection fraction, left ventricular short-axis fractional shortening, peak calcium transient amplitude, and shortening the calcium transient decay time.

6.Antibacterial and Antiviral Effects

Modern research has uncovered the antibacterial and antiviral properties of Codonopsis Radix. In vitro antibacterial experiments have shown that the ethanol extract of Codonopsis Radix exerts significant inhibitory effects against common bacteria such as Staphylococcus aureus, Bacillus subtilis, Bacillus anthracis, Escherichia coli, and Salmonella typhimurium. Additionally, polysaccharides from Codonopsis Radix have been found to reduce the expression level of IFN-β, thereby inhibiting the virulence of duck hepatitis A virus.

7.Antitumor Effects

The aqueous extract of Codonopsis Radix promotes apoptosis in HL-60 cells. The saponins in Codonopsis Radix inhibit the proliferation of human hepatocellular carcinoma cells, including HepG2 and SMMC-7721. Water-soluble polysaccharides CPP1a and CPP1c can induce apoptosis in HepG2 cells by upregulating the Bax/Bcl-2 ratio and activating caspase-3. Furthermore, they exhibit certain cytotoxic effects on cervical cancer Hela cells and gastric cancer MKN45 cells. The pectic polysaccharides from Codonopsis Radix have significant cytotoxic effects on human lung adenocarcinoma A549 cells. The acidic polysaccharides of Codonopsis Radix serve as potential candidates for preventing tumor metastasis, inhibiting the invasion, migration, and adhesion of human ovarian epithelial tumor HO-8910 cells.

Clinical Applications

Codonopsis Radix is widely used in clinical practice, where it can be employed to treat cardiovascular diseases, gynecological conditions, and alleviate physical discomfort caused by stress reactions. Additionally, it serves as an adjuvant drug to enhance the efficacy of Western medications and reduce adverse reactions. Due to its ability to replenish the middle and boost qi, Codonopsis Radix is a common choice in the clinical treatment of anemia, demonstrating efficacy in treating anemia of qi and blood deficiency type, spleen-kidney yang deficiency type, liver-kidney yin deficiency type, and kidney deficiency with blood stasis type.

A comparative study was conducted to observe the therapeutic effects of Shengmai Injection alone versus a combination of Shengmai Injection and Dangshen Huangqi Decoction (containing 20g of each of Codonopsis Radix and Rehmanniae Radix, 10g of each of Ophiopogonis Radix, Schisandrae Chinensis Fructus, Atractylodis Rhizoma, Phellodendri Chinensis Cortex, Cyathulae Radix, Coicis Semen, Angelicae Sinensis Radix, Chuanxiong Rhizoma, and Glycyrrhizae Radix et Rhizoma, and 5g of Prepared Aconiti Lateralis Radix Praeparata) on intradialytic hypotension (IDH). After one week of treatment, patients' clinical symptoms, systolic and diastolic blood pressures, hemoglobin (Hb) levels, plasma albumin (ALB) levels, C-reactive protein (CRP) levels, and adverse reactions were evaluated as indicators. Statistical analysis indicated that patients who received the combination therapy with Dangshen Huangqi Decoction experienced better treatment outcomes.

Codonopsis Radix has demonstrated proven efficacy in the treatment of digestive system diseases such as chronic atrophic gastritis, Helicobacter pylori-infected gastropathy, and functional dyspepsia with spleen deficiency and liver stagnation syndrome. Furthermore, it has therapeutic applications in the management of acute high-altitude sickness, spontaneous postpartum lactation, schizophrenia (note: the original text "Schizophrenia" likely refers to a medical condition, and I've assumed "schizophrenia" for context), diabetes mellitus complicated with depression, heart failure, renal failure, and functional uterine bleeding.

References:

[1] Wang Han, Lin Hongqiang, Tan Jing, et al. Research Progress on Pharmacological Effects and Clinical Applications of Codonopsis Radix [J]. World Latest Medical Information Digest, 2019, 19(07): 27-28+30.

[2] Xie Qi, Cheng Xuemei, Hu Fangdi, Wang Changhong. Research Progress on Chemical Constituents, Pharmacological Effects, and Quality Control of Codonopsis Radix [J]. Shanghai Journal of Traditional Chinese Medicine, 2020, 54(08): 94-104.

About the Author

Xiaonisha, a food technology professional holding a Master's degree in Food Science, is currently employed at a prominent domestic pharmaceutical research and development company. Her primary focus lies in the development and research of nutritional foods, where she contributes her expertise and passion to create innovative products.