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Due to lifestyle changes, modern society sees a rapid increase in obesity occurrence along with an aggravated risk of metabolic syndromes in the general population, including diabetes, hepatic steatosis, cardiovascular diseases and certain types of cancer. Although obesity has become a serious worldwide public health hazard, effective and safe drugs treating obesity are still missing. Traditional Chinese medicine TCM has been implicated in practical use in China for thousands of years and has accumulated substantial front line experience in treating various diseases.

Compared to western medicine that features defined composition and clear molecular mechanisms, TCM is consisted with complex ingredients from plants and animals and prescribed based on overall symptoms and collective experience. Because of their fundamental differences, TCM and western medicine were once considered irreconcilable. However, nowadays, sophisticated isolation technologies and deepened molecular understanding of the active ingredients of TCM are gradually bridging the gap between the two, enabling the identification of active TCM components for drug development under the western-style paradigms.

Thus, studies on TCM open a new therapeutic avenue and show great potential in the combat against obesity, though challenges exist. In this review, we highlight six key candidate substances derived from TCM, including artemisinin, curcumin, celastrol, capsaicin, berberine and ginsenosides, to review their recent discoveries in the metabolic field, with special focus on their therapeutic efficacy and molecular mechanisms in treating obesity and metabolic diseases.

In addition, we discuss the translational challenges and perspectives in implementing modern Chinese medicine into the western pharmaceutical industry. For thousands of years, before the introduction of western medicine, Chinese people relied on traditional Chinese medicine TCM to treat diseases and relieve discomfort.

However, in the modern society, with the prevalence of western medicine, which is developed under strict experimental proofs and feature clear-cut molecular compositions and mechanisms of action, TCM meets serious criticisms and challenges due to undefined compositions and unclear therapeutic mechanisms Qiu, Fortunately, nowadays, sophisticated isolation techniques have enabled scientists to identify active ingredients from TCM to elucidate the molecular mechanisms of their therapeutic effects, thus promote the re-discovery of ancient TCM compounds to be potentially developed as drugs under western medical standard.

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A few promising TCM compounds with successful implications include, but not limit to, artemisinin in treating malaria Liu et al. Looking back into the history of human diseases, before the enlightenment of modern medicine and vaccinology, infectious disease outbreaks decimated large populations and were once the most threatening events to mankind.

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Among them, obesity holds special importance as it is a major risk factor for many other metabolic diseases, i. Briefly, obesity is an excessive deposit of white fat in the body. The abnormal accumulation of fat poses adverse impacts on the metabolic fitness of the body and is positively associated with aberrant metabolic complications including hyperglycemia, insulin resistance, dyslipidemia, hypertension Bays and Dujovne, and chronic low-grade inflammation Saltiel and Olefsky, Fat tissues are metabolically active organs and are classified as white, brown and beige fat based on their morphology, physiology and functions Boss and Farmer, ; Xu et al.

Together they maintain the energy balance of the body with white fat storing energy in forms of triglycerides, while brown and beige fat dissipating energy for thermogenesis via UCP1 activation. Considering different therapeutic leads, compounds derived from TCM possess two major advantages over synthetic drugs in treating obesity.

First, obesity is a complex disease that shows no clear pathogens and its pathogenesis involves multiple genetic factors and signaling networks. In patients with obesity and metabolic diseases, multiple organs, i.

A Natural Guide to Weight Loss That Lasts

In this sense, the concept of TCM emphasizes the holistic treatment of a disease. Studies on TCM have demonstrated that their active ingredients target multiple organs and tissues in the body to exert systemic effects, which match the characteristics of obesity. Second, obesity and metabolic diseases are not as immediately crippling or death threatening as infectious diseases. Patients require long-term care and persistent treatment to prevent advance disease progression, which greatly burdens their family and the society as a whole.

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Thus, it is important to take long-term effectiveness and safety into account when developing drugs for obesity. These characteristics make TCM a promising source for new drug development for obesity and metabolic diseases. However, putting their appealing efficacies aside, the caveat is that much of TCM has unclear compositions and vague mechanisms, which not only hinders their wide application into modern clinic, but can sometimes be detrimental.

One extreme case is the recently reported implication of aristolochic acids and similar compounds from Aristolochia and related plant in liver cancers in Asia population for their mutagenesis attribution Ng et al. During this process, various factors like therapeutic mechanism, clinical data, development cost, etc.

TCM: A Natural Guide to Weight Loss That Lasts (eBook) by Nan Lu, Ellen Schaplowsky (Author)

In recent years, great interests have been focused on TCM, producing a substantial amount of research data. In this review, we highlight recent studies of six promising TCM compounds in the metabolic aspect based upon their clinical, mechanistic properties or current application, including artemisinin, curcumin, celastrol, capsaicin, berberine and ginsenosides.

Substantial data demonstrates their effectiveness and low adverse effects in various diseases, promoting a few into pre-clinical or clinical trials, though not all trials gave consistent results. Artemisinin is derived from the sweet wormwood Artemisia annua L. Artemisinin and its semi-synthetic derivatives-based therapy are currently the standard and the most effective treatment for uncomplicated Plasmodium falciparum malaria. In , Dr. Youyou Tu was awarded the Nobel Prize for medicine for discovering and isolating artemisinin.

This makes artemisinin the most acknowledged and successful TCM compound. Aside from malaria, in recent years, with the spike in overweight and obesity rate, more and more attentions are focusing on the roles of artemisinin and its derivatives in treating obesity and metabolic diseases. In addition, since the groundbreaking discovery of brown and beige fat in human adults, activation of brown fat and browning of white fat, two major sources of adaptive thermogenesis and important outputs for energy expenditure, have emerged as potential therapeutic means to treat obesity and metabolic diseases Cypess and Kahn, ; Boss and Farmer, Further examination reveals artemisinin and other artemisinin derivatives, dihydroartemisinin, artesunate and arteether, could also promote browning.

Importantly, local delivery of artemether into subcutaneous fat or systemic delivery via tail vein in mice effectively reduces high fat diet induced body weight gain, enhances cold tolerance and improves insulin sensitivity. In another study, it is reported that leaf extracts of Artemisia annua, the source of artemisinin, attenuates hepatic steatosis and inflammation in diet-induced obese DIO mice Kim et al.


These studies shed first light on the possibility of exploiting artemisinin and its derivatives as an anti-obesity and anti-fatty liver drug in vivo , though detailed mechanistic study and clinical data are warranted. As a paradigm of the translational application of TCM, continued characterization of the metabolic properties of artemisinin and its derivatives would bring hope to patients with obesity and metabolic diseases.

In sharp comparison with artemisinin, whose effectiveness is well acknowledged in academia, curcumin may be the most controversial TCM compound in the eyes of western chemists and biologists. Curcumin is the principal curcuminoid in the turmeric of the ginger family. The contradictions are probably due to the poor solubility of curcumin in aqueous solution, thus limiting its bioactivity and stability in many studies Nelson et al. But on the other hand, it is of major concern that curcumin fluoresces naturally, which may interfere with drug screening that relies highly on fluorescence signals, producing screen artifacts and generating false positive results Baker, Thus, any attempt at the pharmacological use of curcumin should take these factors into account.

In the metabolic aspects, in adipocytes, consistent reports indicate that curcumin suppresses adipocyte differentiation by affecting classic regulators of adipogenesis Ejaz et al. Curcumin also ameliorates hypoxia-induced insulin resistance and inflammation in 3T3-L1 adipocytes Priyanka et al.

In the browning process, it has been shown that curcumin treatment induces browning in primary white adipocytes and adipose tissues and augments thermogenic and mitochondrial gene programs in a classic norepinephrine dependent manner Wang et al. In rodents, curcumin treatment enhances energy expenditure in DIO murine models and protects against weight gain and inflammation of adipose tissues Weisberg et al.

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In a few clinic trials, curcumin has been shown to improve insulin resistance and hyperlipidemia in patients with metabolic syndromes Mohammadi et al. Importantly, the resolution to the predicament of insolubility and instability of curcumin, which hinders its clinical application, may lie in the researches of curcumin analogs. C66, a novel curcumin derivative, inhibits JNK phosphorylation, reduces high glucose-induced inflammation in cardiomyocytes and prevents the development of diabetic cardiomyopathy in mice Pan et al.

Alternatively, nano-formulated curcumin generated using nanoparticles has shown improved bioactivity and efficacy compared to native curcumin in various in vitro and in vivo disease models, indicating its potential implication in metabolic studies Rahimi et al. However, despite the metabolic benefits in curcumin-treated adipocytes and mice models, these studies lack detailed mechanisms and target molecules.

Further mechanistic investigations are needed to disperse the controversy around curcumin before it can be further implicated in the treatment of obesity and metabolic diseases. Mechanistic studies are vital in drug development to prevent potential side effects. Compounds with single targets are favored by scientists for their balanced efficacy and safeness, although compounds with multiple targets in multiple organs could be of potential interest in treating obesity and metabolic diseases since the patients usually feature pathological changes in not one but multiple organs, i.

As an example, celastrol is a TCM compound targeting multiple metabolic organs with detailed mechanisms of action deciphered Liu et al. Celastrol tripterine is a chemical compound isolated from the root extracts of Tripterygium wilfordii Thunder god vine, TGV. Recently, a series of studies have brought celastrol onto the metabolic stage and highlight it as a versatile regulator of obesity and metabolic diseases with both central and peripheral targets.

Centrally, Liu et al. Another report from Luo et al. Apart from its impact on obesity and metabolic diseases through inflammatory inhibition in multiple organs, celastrol also exerts its beneficial effects by directly promoting energy expenditure. HSF1 is a classic transcription factor induced by multiple stimuli, including heat shock, oxidative and mechanical stresses Anckar and Sistonen, It orchestrates the function of heat shock proteins in protein refolding and damage repair, thus is vital for protein homeostasis and cell survival Gomez-Pastor et al.

Based on these preliminary data and the fact that celastrol is derived from TCM with wide application in humans, Ma et al. It has been shown that celastrol targets multiple organs and improves their metabolic performances simultaneously, thus rendering it a TCM compound with comprehensive effects in treating obesity and metabolic diseases Ma et al.

Future work could be focused on its structural modification to obtain celastrol derivatives that preferentially target specific organs.

Besides, it is of note that triptolide, another major active component of Tripterygium wilfordii, shows similar anti-inflammatory and anti-cancer effects to celastrol Li et al. Combined treatment of triptolide and celastrol shows synergistic effects in suppressing tumor cell growth in vitro Jiang et al.

It would be worthwhile to test their synergistic effects in the treatment of obesity and metabolic diseases. Finally, although celastrol treatment of various concentrations and lengths of time shows no overt side effects or toxicity in rodents, low sperm density and some toxicity are reported in male patients treated with TGV for rheumatoid arthritis Lopez et al. Future studies are warranted to elucidate the efficacy and a safe concentration of action for celastrol and other TGV constituents in clinic.

One hundred years ago, Capsaicin was identified and purified as one of the major active biological components of peppers Capsicum. They also have longtime use in TCM to relieve physical pain and treat gastrosis, detrusor hyperreflexia and rheumatic arthritis. Among active TCM compounds translated for pharmaceutical use, capsaicin is one of the best examples featuring extensively studied molecular targets and mechanisms. Unlike celastrol, which exerts its function through multiple targets in diverse organs, capsaicin functions through a single and clear target, its receptor TRPV1 Caterina et al.

It is a prime target for pain relief upon activation by capsaicin, as well as thermal heat, acidic conditions and allyl isothiocyanate Gavva, With the accumulation of evidence about the regulatory function of TRPV1 in the central nervous system for food intake and body temperature, as well as in peripheral organs for insulin and adipokine secretion, agonist-mediated TRPV1 desensitization begins to attract attention for its potential application in metabolic field.

Capsaicin, as the classical TRPV1 agonist, has been shown in human and in rodents to increase satiety, reduce food intake, increase sympathetic nervous system activity Reinbach et al.