Herbal Medicine in the Treatment of Patients with Type 2 Diabetes Mellitus
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, insufficient insulin secretion, and insulin resistance. It is a significant global health challenge, with an increasing prevalence and substantial economic and human health losses. According to the International Diabetes Federation (IDF), the global prevalence of diabetes among adults aged 20–79 was 8.8% in 2017, affecting 425 million people. This number is projected to rise to 629 million by 2045. Alarmingly, approximately half of all adult patients with diabetes remain undiagnosed, and in 2017, around 4 million adults died from diabetes-related complications, with 46.1% of these deaths occurring before the age of 60. T2DM accounts for about 95% of all diabetes cases and is associated with severe complications that can lead to death. Therefore, the primary goal of T2DM treatment is to prevent or delay the onset of complications by maintaining blood glucose levels within the normal range. Current treatment strategies include lifestyle interventions, oral medications, injected drugs, surgical treatments, and complementary and alternative therapies.
Herbal medicine has been used in traditional Chinese medicine (TCM) for over 1500 years to treat diabetes, referred to as “Xiao-Ke disease” in ancient Chinese texts. Recent research has demonstrated the efficacy of herbal medicine in managing T2DM through various mechanisms, including anti-inflammatory effects, antioxidant properties, regulation of blood lipid metabolism, and anti-glucose effects. This article comprehensively reviews the therapeutic actions of herbal medicine in T2DM, focusing on these mechanisms.
Anti-Inflammatory Effects
Chronic low-grade inflammation is a hallmark of T2DM, characterized by increased production of pro-inflammatory cytokines such as interleukin-1b (IL-1b), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a). These cytokines contribute to pancreatic beta-cell damage and insulin resistance, making the inhibition of inflammatory cytokines a crucial step in T2DM treatment. Herbal medicine has shown promise in this regard.
For instance, Memecylon umbellatum, a plant from the Melastomataceae family, has been shown to reduce serum IL-6 levels and insulin resistance in high-fat diet-induced obese mice. The nuclear transcription factor kappa B (NF-kB) plays a central role in the inflammatory response by regulating gene expression. Blocking the NF-kB signaling pathway can effectively reduce the production of pro-inflammatory cytokines. Lycii Radicis Cortex, derived from Lycium barbarum or Lycium chinense, has been found to inhibit NF-kB activity, thereby reducing inflammation. Similarly, S-[6]-Gingerol, a compound found in ginger, suppresses cyclooxygenase 2 (COX2) expression by blocking the NF-kB pathway, reducing IL-6 and IL-8 levels in cytokine-stimulated cells.
Momordica charantia, commonly known as bitter melon, has been used in Asia for its hypoglycemic effects. Studies have shown that bitter melon powder inhibits NF-kB activation by preventing the degradation of the NF-kB inhibitor (IkBa), thereby reducing inflammation. JinQi-JiangTang tablets, a Chinese patent medicine containing extracts from Astragalus membranaceus, Coptis chinensis, and Lonicera japonica, also inhibit NF-kB activity by reducing IkBa degradation. These findings highlight the potential of herbal medicine in mitigating inflammation in T2DM.
Antioxidant Properties
Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, is a significant contributor to T2DM pathogenesis. Pancreatic beta-cells are particularly vulnerable to oxidative stress due to their low antioxidant enzyme activity. Herbal medicine has demonstrated antioxidant effects by enhancing the activity of enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-px), and catalase (CAT).
Tinospora cordifolia, a plant from the Menispermaceae family, has been shown to increase SOD and CAT activities in diabetic rats. Jiao-Tai-Wan, a traditional Chinese herbal formula consisting of Rhizoma coptidis and Cinnamomum cassia, also exhibits antioxidant properties by increasing the activities of SOD, GSH-px, and CAT. The Jiang Tang Xiao Ke (JTXK) granule, a Chinese patent medicine containing Radix Salviae Miltiorrhizae, Radix Rehmanniae, Panax ginseng, R. coptidis, and Fructus corni, has been found to improve antioxidant capacity in diabetic mice when combined with metformin.
Nitric oxide (NO) is another mediator of oxidative stress, and its production is regulated by inducible nitric oxide synthase (iNOS). Inhibition of iNOS can reduce oxidative stress. JinQi-JiangTang tablets have been shown to reduce iNOS activity in insulin-resistant cells. Glabridin, a compound derived from licorice root, also inhibits iNOS expression in macrophage-like cells. Additionally, the aquatic extract of Stevia has been found to decrease malondialdehyde (MDA) levels, a marker of lipid peroxidation, indicating its antioxidant potential.
Regulation of Blood Lipid Metabolism
Lipotoxicity, resulting from lipid metabolism disorders, contributes to insulin resistance and pancreatic beta-cell dysfunction in T2DM. Herbal medicine has been shown to regulate blood lipid levels by reducing triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) while increasing high-density lipoprotein (HDL).
Folium Mori extract, derived from Morus alba, has been found to reduce serum TG, TC, and LDL levels in diabetic rats. Qurs Tabasheer, a polyherbal formulation containing Portulaca oleracea, Rosa damascene, Punica granatum, Bambusa arundinacea, and Lactuca sativa Linn, has been shown to lower TG and TC levels in diabetic rats. Tang-kang-fu-san, a Tibetan herbal formula, effectively reduces serum TG and LDL levels while increasing HDL levels in diabetic mice.
Free fatty acids (FFA) play a role in TG synthesis, and their reduction can improve lipid metabolism. An aqueous extract of herbal compounds containing Pueraria lobata, Panax ginseng, Rehmannia glutinosa, Poncirus fructu, Dioscorea batatas, Evodia officinalis, and Amomum cadamomum has been shown to decrease plasma FFA levels. Acetyl-coenzyme A carboxylase (ACC) is an enzyme involved in fatty acid metabolism, and its inhibition can reduce FFA levels. Polygonum hypoleucum extract has been found to inhibit ACC in high-fat diet-induced obese mice. Ginseng, a widely used herb, has been shown to reduce TG and TC levels in diabetic rats by attenuating acetyl-coenzyme A acetyltransferase 2 (ACAT2) activity.
Anti-Glucose Effects
Maintaining blood glucose levels within the normal range is a critical aspect of T2DM management. Herbal medicine has been shown to exert anti-glucose effects through various mechanisms, including the inhibition of alpha-amylase and alpha-glucosidase, enzymes involved in carbohydrate digestion, and the enhancement of glucagon-like peptide-1 (GLP-1) secretion.
Okchun-san, a Korean herbal formula, has been found to lower blood glucose levels in diabetic mice. Bofu-tsusho-san, a Japanese herbal formula, has been shown to reduce hyperglycemia in diabetic mice. Alpha-amylase and alpha-glucosidase inhibitors can reduce postprandial hyperglycemia. Acer pycnanthum extract has been found to inhibit alpha-glucosidase, thereby lowering blood glucose levels. Lodhrasavam, an Ayurvedic formulation, has been shown to inhibit both alpha-amylase and alpha-glucosidase, making it effective in managing postprandial hyperglycemia.
GLP-1 is a peptide that promotes insulin secretion in response to elevated blood glucose levels. [6]-Gingerol has been shown to enhance GLP-1-mediated insulin secretion in diabetic mice. The Daming capsule, a Chinese patent medicine, has been found to increase GLP-1 secretion in diabetic mice. Dipeptidyl-peptidase 4 (DPP-4) is an enzyme that degrades GLP-1, and its inhibition can enhance GLP-1 activity. Sitagliptin, a DPP-4 inhibitor, is widely used in T2DM treatment. An herbal formula containing Coptis chinensis, Morus alba leaves, Schizandra chinensis, and Psidium guajava has been shown to inhibit both alpha-glucosidase and DPP-4, offering a dual mechanism for blood glucose control.
Other Effects
Herbal medicine also exerts therapeutic effects on T2DM through other mechanisms, such as modulating the gut microbiome and enhancing adiponectin expression. The gut microbiome plays a crucial role in insulin resistance and T2DM pathogenesis. Ephedra sinica has been shown to reduce fasting blood glucose levels by altering the composition of gut microbiota. The Qijian mixture, a new herbal formula containing Ramulus euonymi, Pueraria lobata, Astragalus membranaceus, and Coptis chinensis, has been found to enrich Bacteroidetes in the gut microbiome, potentially contributing to its anti-diabetic effects.
Adiponectin, a cytokine secreted by adipocytes, improves insulin resistance. Herbal medicine has been shown to enhance adiponectin expression. Flavones isolated from Cirsium japonicum DC have been found to increase adiponectin expression in diabetic rats. Dangguiliuhuang decoction, a traditional Chinese herbal formula, has been shown to increase adiponectin expression, contributing to its anti-diabetic effects.
Conclusion
T2DM is a global health challenge that requires comprehensive management strategies. Herbal medicine offers a holistic approach to T2DM treatment through its anti-inflammatory, antioxidant, blood lipid-regulating, and anti-glucose properties. While the efficacy of herbal medicine in T2DM management has been demonstrated in various studies, further research is needed to identify active and toxic components, conduct large-scale clinical trials, and evaluate long-term outcomes. Herbal medicine represents a promising complementary and alternative treatment for T2DM, with the potential to address multiple aspects of the disease.
doi.org/10.1097/CM9.0000000000000006
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