Diabetes is an endocrine and metabolic disorder disease characterized by increase of plasma glucose level, and is called the three worldwide diseases together with cancers and cardiovascular diseases. According to the report of the International Diabetes Federation in 2017, there were about 451 million diabetes patients in the world, and the number is expected to skyrocket to 693 million in 2045. Diabetes is mainly divided into type 1 diabetes and type 2 diabetes: type 1 diabetes is an autoimmune disease that results from the destruction of pancreatic β cells, which 5%~10% diabetes patients have and is mainly treated depending on insulin, with the long-acting  sustained-release preparations being the R&D focus of the pharmaceutical companies; 90% type 2 diabetes (T2DM) is a result of gene and environment, of which the main pathological mechanism is insulin resistance and the incidence has shown a rapid growing trend in recent years. In terms of T2DM treatment, the hypoglycemic effects of Western medicines are significant, however, long-term use will easily cause many adverse reactions such as ketoacidosis, obesity, hypoglycemia, and cardiovascular diseases.

TCM compound preparations lay emphasis on holistic treatment, have many active ingredients, and can intervene with the disease occurrence and development through additive effect for a single target, multi-target synergistic effect, and toxicity dispersion effect, to produce the therapeutic effect of toxicity reducing and efficacy enhancing; they are especially applicable to intervening with the occurrence and development of complex T2DM jointly affected by gene and environment factors. Seeking new diabetes drugs from TCM compound preparations has become a new direction in hypoglycemic drug R&D. Diabetes treatment with TCM compound preparations mainly includes classic compound preparations, modern compound preparations, and TCM and Western medicine compound preparations.

In TCM syndrome differentiation and treatment, many classic formulas are used to treat Xiaoke disease, of which the pathogenesis is overall root deficiency and branch excess, and clinical manifestation is mostly "polydipsia, polyphagia, polyuria, and emaciation", similar to modern diabetes. In the classic formulas, besides Liu Wei Di Huang Wan (Six-Ingredient Pill with Rehmannia) and other liver and kidney nourishing compound preparations that have certain hypoglycemic effects in the long-term use, the TCM classic formulas much studied in recent years also include Huanglian Jiedu Decoction, Gegen Qinlian Decoction, and Buyang Huanwu Decoction, etc. The occurrence and development of diabetes involve a long-term process and experience the change from heat to deficiency: for example, Huanglian Jiedu Decoction and Gegen Qinlian Decoction clear stomach heat and benefit bowel moisture at the stage of heat, and Buyang Huanwu Decoction invigorates qi and promotes blood circulation at the stage of deficiency. Huanglian Jiedu Decoction stems from the Handbook of Prescriptions for Emergency; it is prepared from coptidis rhizoma, Radix Scutellariae, Cortex Phellodendri, and Fructus Gardeniae, has the efficacy of clearing away heat and toxic materials, and is indicated for Sanjiao Heat Toxin Syndrome; its main component is coptidis rhizome, and the main active ingredients for reducing blood glucose are alkaloids like berberine, jatrorrhizine, and coptisine, and flavonoids like baicalin, baicalein, and wogonoside. Gegen Qinlian Decoction stems from Zhang Zhongjing’s Treatise on Febrile and Miscellaneous Diseases: Differentiation of the Pulse, Symptom Complex, and Treatment of the Taiyang (Initial Yang) Syndromes, is prepared from kudzu root, Radix Scutellariae, coptidis rhizome, and radix glycyrrhizae, has the efficacy of relieving superficies and clearing interior, and is indicated for diarrhea due to interior cold and exterior heat; its main active ingredients for lowering blood glucose and lipid are flavonoids like puerarin and baicalin and alkaloids like berberine, coptisine, and jatrorrhizine. Buyang Huanwu Decoction is prepared from Astragali Radix, Angelicae Sinensis Radix, red peony root, earthworm (without earth), Ligusticum wallichii, flos carthami, and peach seed, has the efficacy of invigorating qi and promoting blood circulation and dredging collaterals, and is indicated for qi-deficiency and blood-stasis syndrome in stroke; its main active ingredients for reducing blood glucose and antioxidation are flavonoids and terpenoids: calycosin-7-O-β-D-glucoside, paeoniflorin, and astragaloside.

Modern compound preparations optimize traditional ancient formulas according to patients’ symptoms under the guidance of the TCM theories and improve efficacy of clinical treatment of diabetes and its complications, with the principles of formulating prescription fully showing the characteristics of mechanism complementation and alliance between effective formulas. Take  Jinqi hypoglycemic tablets and Yangyin hypoglycemic tablets for instance. Jinqi hypoglycemic tablets is a pure TCM preparation with honeysuckle, astragalus, and coptidis rhizome and has efficacy of clearing heat and tonifying qi and helping produce saliva and slake thirst, with hypoglycemic ingredients associated with astragalus polysaccharide, astragaloside, chlorogenic acid, and coptidis rhizome alkaloid. Yangyin hypoglycemic tablets is prepared from astragalus, radix codonopsis, kudzu root, fructus lycii, radix scrophulariae, polygonatum odoratum, radix rehmanniae, rhizoma anemarrhenae, cortex moutan, Ligusticum wallichii, polygonum cuspidatum, and fructus schizandrae, etc., has efficacy of invigorating qi and nourishing yin and clearing heat and promoting blood circulation, and can treat T2DM patients with deficiency of qi and yin and deficiency of yin and excess of heat, with main active ingredients being flavonoids, anthraquinones, and phenylpropionic acid: puerarin, emodin, polydatin, and ferulic acid.

The disclosed TCM and Western medicine compound hypoglycemic preparations (private addition of Western medicine preparation into hypoglycemic TCM preparation) that meet the pharmaceutical product regulatory requirements in China are not common, with the representative drug being the Xiaoke Pill. Xiaoke Pill is prepared from astragalus, radix rehmanniae, radix trichosanthis, kudzu root, fructus schizandrae, Chinese yam, and stigma maydis and the Western medicine glibenclamide. From the perspective of TCM, Xiaoke Pill has efficacy of nourishing yin and strengthening kidney and supplementing qi and promoting the production of body fluid, etc.; from the perspective of Western medicine, the quantitative glibenclamide in Xiaoke Pill has a potent hypoglycemic effect, and can reduce glucose toxicity, protect pancreatic β-cell function, and improve patients’ lassitude, asthenia, polyphagia, and liability to feel hungry, etc.

With the continued approval for clinical trials and marketing of Western compound hypoglycemic drugs, compound hypoglycemic preparations have been shown to be more effective in the long-term treatment of diabetes affected jointly by gene and environment. The relevant TCM compound preparations contain many hypoglycemic active ingredients such as alkaloids, flavonoids, terpenoids, and polysaccharides, strengthen insulin sensitivity through regulating glucolipid metabolism, inflammatory pathway, oxidative stress, and amino acid metabolism, and  repairing and regenerating pancreatic β-cells, etc., and achieve coordination and complementation hypoglycemic mechanisms and alliance of effective ingredients, to reduce toxicity and enhance efficacy. Therefore, TCM hypoglycemic compound preparations have become a focus of diabetes drug R&D in China.

References:

[1] Shi Xiuming, Xu Guoliang, Li Yu, et al. Progress of Research on Diabetes Treatment with TCM [J]. Jiangxi Journal of Traditional Chinese Medicine, 2015(5):64-70.

[2] Wu Qinghua, Li Bingtao, Tu Jun. Progress of Research on Diabetes Treatment with Compound TCM [J/OL]. China Journal of Chinese Meteria Medica

About the author: Xiaonisha, a practitioner in food science and technology, graduated from School of Food Science and Engineering in South China University of Technology as a Master of Food Science, and now works at a large drug R&D company in China, engaging in R&D of nutritional food.

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