Could Natural Products Help in the Control of Obesity? Current Insights and Future Perspectives

Obesity is a global issue faced by many individuals worldwide. However, no drug has a pronounced effect with few side effects. Green tea, a well-known natural product, shows preventive effects against obesity by decreasing lipogenesis and increasing fat oxidation and antioxidant capacity. In contrast, other natural products are known to contribute to obesity. Relevant articles published on the therapeutic effect of natural products on obesity were retrieved from PubMed, Web of Science, and Scopus. The search was conducted by entering keywords such as “obesity”, “natural product”, and “clinical trial”. The natural products were classified as single compounds, foods, teas, fruits, herbal medicines—single extract, herbal medicines—decoction, and herbal medicines—external preparation. Then, the mechanisms of these medicines were organized into lipid metabolism, anti-inflammation, antioxidation, appetite loss, and thermogenesis. This review aimed to assess the efficacy and mechanisms of effective natural products in managing obesity. Several clinical studies reported that natural products showed antiobesity effects, including Coffea arabica (coffee), Camellia sinensis (green tea), Caulerpa racemosa (green algae), Allium sativum (garlic), combined Ephedra intermedia Schrenk, Thea sinensis L., and Atractylodes lancea DC extract (known as Gambisan), Ephedra sinica Stapf, Angelica Gigantis Radix, Atractylodis Rhizoma Alba, Coicis semen, Cinnamomi cortex, Paeoniae radix alba, and Glycyrrhiza uralensis (known as Euiiyin-tang formula). Further studies are expected to refine the pharmacological effects of natural products for clinical use.


Introduction
Obesity is an excessive accumulation of fat, which poses a potential health risk.Specifically, a body mass index (BMI) of >30 is considered obese [1,2].Currently, >1 billion individuals are obese globally [3].This number is still increasing [3], meaning that an increasing number of individuals are becoming susceptible to many serious diseases, such as hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, stroke, osteoarthritis, and cancer, due to this chronic and relapsing disease [4].
One typical treatment for obesity is weight loss drugs approved by the US Food and Drug Administration, including orlistat, phentermine-topiramate, and naltrexonebupropion.Chemical medications can help lose weight and maintain weight loss but can also cause changes in behavior [5].However, weight-loss drugs have been withdrawn from the market because of side effects [6].Among those still in use, orlistat, naltrexonebupropion, phentermine-topiramate, liraglutide, and semaglutide have been used for long-term treatment.In contrast, others are only used for short-term treatment due to unguaranteed safety over longer periods [5].Even these drugs may show adverse effects in some individuals and can be inaccessible because of high prices [6].
Therefore, developing new drugs, including botanical drugs, phytomedicines, traditional medicines, and herbal medicines, has gained importance.They have been suggested as substitutes for chemical drugs to reduce side effects while maintaining effectiveness.For example, Ephedrae herba showed preventive effects against hyperlipidemia in mice, possibly by regulating DNA repair and modulating the expression of genes and proteins related to energy metabolism [7].
Therefore, this study aimed to identify natural products that are effective against obesity and examine their effects.After listing the substances tested in clinical trials, we divided them into seven groups: single compound, food, tea, fruit, herbal medicine-single extract, herbal medicine-decoction, and herbal medicine-external preparation.The related studies' results were examined to estimate each group's effectiveness.

Methods
Relevant articles published between 2016 and 2022 on the therapeutic effect of natural products on obesity were retrieved from PubMed, Web of Science, and Scopus.The search was conducted using keywords such as "obesity", "natural product", and "clinical trial".More than one hundred studies were retrieved.We excluded reviews, duplicate articles, studies not written in English, studies with an English abstract but no English full text, studies on patients with obesity but not treating obesity, and studies reporting no significant effect on obesity.Overall, 66 studies demonstrating the efficacy of using natural products to treat obesity were selected for this review.

Obesity Treating Natural Products
Many published studies show that diverse natural products are effective in treating obesity.In this review, natural products were classified into five categories based on the form of the experimental drug: single compound, food, tea, fruit, and herbal medicine.Then, herbal medicine was reclassified into three subcategories based on the type used in the experiments: single extract, decoction, and external preparation.

Single Compound
One study with a single compound showed antiobesity effects (Table 1).Diethyl azelate (DEA) is naturally produced in animals and plants and can be used to improve related metabolic syndromes [8].Steeper et al. reported that daily oral DEA decreased total cholesterol (TC) and low-density lipoprotein (LDL) levels in human males who were overweight, alleviating obesity.This study on DEA included 17 participants and lasted for 21 days.More reliable results would have been drawn if this study had enrolled more subjects.This study's design also decreased its reliability; it used a 21-day prospective design in a before-after clinical trial and did not use blinding or a placebo control during treatment.
It was impossible to determine the trend of studies regarding the antiobesity effects of single compounds because there was only one study in this category.↓ TC/HDL ratio, LDL/HDL ratio, noncholesterol HDL/HDL ratio [8] TC, total cholesterol; HDL, high-density lipoprotein; LDL, low-density lipoprotein.↓, decrease.
Matured H. lupulus L. (hop) bitter acids attenuated diet-induced body fat (BF) accumulation in rodents by enhancing thermogenesis in brown adipose tissue (BAT) through the activity of sympathetic nerves innervating BAT [19] [26].However, polymorphisms in perilipin 4 (PLIN4; −11482G > A), FM and obesity-associated (FTO; rs9939609 (A/T)), and β-adrenergic receptor 3 (ADRB3; Trp64Arg) attenuated its lipolysis effect.Farhat et al. reported that S. rebaudiana (stevia) intake did not result in energy compensation during lunch or throughout the day and reduced postprandial glucose levels compared to sugar [27].Stevia was found to lower appetite and stop the increase in food intake.Leverrier et al. reported that 500 mg/day of H. annuus (sunflower) seed extract for 12 weeks decreased cholesterol, long-lasting LDL, BW, BMI, and WC [28].The intervention was especially effective in females with obesity aged >30 years.
Six weeks of C. lanatus (watermelon) supplementation increased fasting plasma L-arginine, cis-lycopene, and trans-lycopene levels and decreased vascular cell adhesion molecule 1 (VCAM1) levels [29].This study only suggested indirect effects on obesity, so further research is needed to obtain effective results for lipid metabolism.A new comprehensive study by Permatasari et al. showed that C. racemosa (green seaweed or green algae) could be a new candidate for antiobesity functional food [30].This study integrated in silico and in vitro experiments with a four-week, randomized, double-blind, placebo-controlled clinical trial.A randomized, double-blind, parallel-group, placebo-controlled pilot study by Majeed et al. demonstrated the antiobesity potential of C. rotundus extract (CRE) [31].Interestingly, CRE showed antiadipogenic activity, was safe for human consumption, and effectively managed weight and hypercholesterolemia in individuals with overweight.
The main active ingredient in Malabar tamarind extract is HCA, which is known to attenuate weight gain and fat synthesis in animals and humans [32].However, the mechanism underlying the action of HCA is not fully understood.A three-month clinical study on 100 individuals with obesity and a subsequent computational study investigated the effect of HCA treatment on anthropometric measurements and plasma lipid profiles in human subjects [32].They showed that HCA could reduce weight gain and fat accumulation in subjects with obesity.Han et al. conducted a randomized, double-blind, placebo-controlled study assessing the effect of standardized H. serrata (Thunb.)Ser.leaf extract (WHS) on BW and BF reduction in human subjects with overweight or obesity [33].Daily WHS supplementation reduced BW, BMI, and BFM.Interestingly, this was accompanied by reduced HC, VFA, abdominal fat area, and the visceral-subcutaneous ratio.More interestingly, no significant side effects were observed during or after 12 weeks of this intervention.
All the above studies support the claim that certain foods help prevent obesity.Foods used in these studies were usually also treated as herbal medicines, and many processed foods into extracts to test their effects on obesity.Certain foods reduce obesity usually by controlling metabolic hormones or reducing appetite.Most studies stated that there were no side effects.However, some studies used noodle or snack forms to test the food's antiobesity effect [13,17].Moreover, some studies did not clearly indicate a mechanism for reducing obesity.Therefore, further studies are needed.

Teas
Twelve human studies treated obesity using tea (Table 3).Yonekura et al. conducted a cross-sectional study on C. arabica (coffee) and C. sinensis (green tea).These substances were administered to 232 Japanese women aged 40-65 years with menopausal symptoms who completed the brief-type self-administered diet history questionnaire [35].Patients were divided into four groups depending on their coffee (CF) and green tea (GT) consumption.Using a multivariate model, they showed an inverse relationship between daily CF/GT intake and BW, BMI, and cardio-ankle vascular index.Ghasemi et al. conducted a clinical trial using combined high-intensity interval training and green tea supplementation in 30 women with overweight [36].They determined that daily green tea consumption increased the levels of sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and catalase (CAT) and significantly decreased BFP, BMI, and BW.Therefore, the catechins in green tea inhibit lipogenesis, increase fat oxidation, and improve antioxidant capacity.Kobayashi et al. conducted a randomized, double-blind, placebo-controlled trial examining the effectiveness of green tea beverages enriched with catechins and a galloyl moiety on obesity in 124 subjects with obesity [37].Green tea catechins with a galloyl moiety reduced BW, BMI, and BFP by decreasing abdominal fat area via inhibiting or attenuating intestinal fat absorption.All these studies support the view that tea is effective in weight loss.Most studies supported green tea's ability to help individuals lose weight; only one study found the beverage ineffective.Therefore, further research on the obesity-reducing effect of green tea is needed.In addition to green tea, coffee, kosen-cha, oolong tea, and puer tea were reported to alleviate obesity.

Fruits
Six studies demonstrated the effectiveness of fruit-derived natural products in ameliorating obesity (Table 4).Duchnowicz et al. reported that A. melanocarpa decreased acetylcholinesterase (AChE) activity and oxidative stress, improving lipid metabolism related to cholinesterase activity [46]. A. melanocarpa at 3 × 100 mg/day for two months decreased cholesterol and lipid peroxidation, reducing AChE.Rondanelli et al. found that bergamot phytosome positively affected VAT after 30 days and remained effective for a further 60 days [47].Bergamot phytosome tablets (500 mg) taken twice daily for 12 weeks modulated lipids, decreasing TC and LDL and increasing HDL.All these studies support the efficacy of fruit-derived natural products against obesity and lipid disorders, although there were some limitations.Treatments in several studies appeared effective but were not significant.In addition, a few studies were conducted on obesity-related bioavailability, such as metabolic disorders, inflammatory status, and antioxidant capacity, rather than on obesity itself.

Herbal Medicines
Herbal medicines have been used to treat various diseases in East Asia for millennia, of which several have antiobesity effects.Here, we divide herbal medicines into three categories: single extracts, decoctions, and external preparations.

Herbal Medicines-Single Extracts
Eight studies examined the antiobesity effects of herbal medicine-single extracts (Table 5).S. maxima extract was reported to influence lipid profiles due to its correlation with reduced LDL [53], providing encouraging results in individuals with obesity when given at 2 g/day for three months.Yousefi et al. compared the effects of S. platensis powder to a control treatment, finding it decreased appetite, BW, BF, BMI, WC, and TG [54].Improvements in individuals with obesity-associated metabolic disorders were noted after 12 weeks of treatment with one S. platensis tablet (2 g) daily.A 12-week study examined the beneficial effects of combining Z. multiflora (ZM) with oxymel on obesity in three groups: 0.75 g ZM in 10 mL oxymel, 1.5 g ZM in 10 mL oxymel, and 10 mL oxymel without ZM [55].It showed reduced WC in all groups, while group A also showed reduced HC, and group B also showed a reduced waist-to-hip circumference ratio.Altogether, these studies provide evidence supporting the antiobesity effects of herbal medicines-single extracts, although they showed similar limitations, including small sample sizes and short observation periods.In addition, only a few studies examined safety and tolerability.Therefore, further follow-up studies are needed to confirm their findings.

Herbal Medicines-Decoctions
Eight studies suggested that herbal medicine decoctions have antiobesity effects in human subjects (Tables 6 and 7).Cheon et al. reported that Euiiyin-tang could significantly reduce weight in patients with obesity after 12 weeks of treatment [60].While both showed reduced weight, the decrease in WC and HC was greater in the Euiiyintang group than in the placebo group.Cho et al. reported that YY-312, an herbal extract powder from I. cylindrica Beauvois, C. unshiu Markovich, and E. officinalis Dode, reduced BF.Administrating 2400 mg/day of YY-312 for 12 weeks significantly reduced BFM, BFP, BW, and WC compared to the placebo [61].Herranz-López et al. investigated the effects of subjects with overweight consuming a combination of polyphenolic LC-HS extracts enriched in polyphenols at a daily dosage of 500 mg for two months while maintaining an isocaloric diet [62].The subjects showed meaningful reductions in BW, abdominal circumference, and BFP.Kudiganti et al. showed that taking 400 mg of Meratrim twice daily for 16 weeks significantly reduced BW, BMI, waist size, and hip size compared to the placebo without supplement-related AEs [63].Dixit et al. reported that receiving 900 mg/day of LI85008F over two doses for 16 weeks significantly reduced BW and BMI compared to the placebo [64].WC, HC, and WHR were also meaningfully reduced.Chung et al. concluded that patients treated with 900 mg/day of Qingxue Dan for eight weeks significantly reduced BMI and TG, with decreases in total BF, abdominal FM (AFM), and WC also noted [65].Adamska-Patruno et al. found that combining M. alba (white mulberry), P. vulgaris (white bean), and C. arabica (green coffee) extracts decreased the adverse effects of high-glycemic index/load meal consumption [66].Lower glucose and insulin levels were observed with both IP-A (a mixture of 400 mg green coffee, 600 mg white mulberry, and 1200 mg white bean extracts) and IP-B (a mixture of 400 mg green coffee, 600 mg white mulberry, and 1200 mg white bean extracts supplemented with 2000 mg inulin and 3000 mg glucomannan) treatments.All these studies commonly suggest that herbal medicine decoctions can reduce obesity.Most studies used BW, BMI, and BFP as indicators of this reduction.However, some did not find significant results for some indicators.Therefore, further studies are needed to confirm their findings.

Herbal Medicines-External Preparations
Seven studies used herbal medicine-external preparations to treat obesity (Table 8).Moszak et al. stated that administering 20 mL/day of A. cruentus (amaranth) seed oil or B. napus (rapeseed) oil generally improved insulin levels and percentage HDL compared to the control treatment [68].However, all three groups showed significantly reduced weight, BMI, WC, HC, FM, lean body mass, visceral FM, and total body water percentage.Escalante et al. reported that topically applying Lipoxyderm, a lotion containing aminophylline, caffeine, Yohimbe, l-carnitine, and C. asiatica (gotu kola), twice daily for 28 days significantly decreased THC, thigh skinfold thickness, and thigh FM compared to the placebo [69].Galvão Cândido et al. concluded that daily high-fat breakfasts containing 25 mL of extra virgin O. europaea (olive) oil over nine consecutive weeks led to higher fat loss [70].Extra virgin olive oil also increased serum creatinine, decreased hepatic alkaline phosphatase, and generally reduced interleukin-1β (IL-1β) levels.Rezaei et al. found that consuming 20 g/day of L. usitatissimum (flaxseed) oil for 12 weeks resulted in greater weight loss and decreased WC than the placebo [71].The intervention proved that flaxseed oil benefits patients with nonalcoholic fatty liver disease when combined with a low-energy diet and moderate physical activity.Lima et al. showed that after receiving 300 g of vegetables and legumes containing varying folate levels and a Corylus (hazelnut) capsule, women with overweight did not show weight loss but did show reduced beta-3 adrenergic receptor (ADRB3) gene methylation and malondialdehyde levels and increased in HDL-C and total antioxidant capacity [72].
Altogether, these studies show that external herbal medicine preparations can help reduce obesity.These studies mainly focused on oils and examined more than one factor.However, some results were not significant, and indicators showed less consistency across studies than in other fields.

Discussion
Obesity is a global burden transcending borders with continuously high prevalence rates [75].While current technologies and synthetic medicines are being adopted to treat obesity, their related complications and safety issues are still being discussed.Traditional herbal medicines have arisen as effective agents to alleviate this multifactorial disease, and various studies have scrutinized the antiobesity effects of natural products.While many systemic reviews have examined the effects of natural products against obesity, none have systematically categorized natural drugs and mechanisms.In addition, this review is the most recent to assess extensive natural products.This review summarizes the effects and related mechanisms of each natural product studied in clinical trials.The natural products were classified into seven groups: natural compounds, foods, teas, fruits, extracts, decoctions, and external preparations.The mechanisms of the natural products were organized into lipid metabolism, anti-inflammation, antioxidant, appetite loss, and thermogenesis.

Antiobesity Mechanism
Based on the reviewed studies, natural products that demonstrated efficacy in alleviating obesity shared common mechanisms.Major mechanisms included lipid metabolism, anti-inflammation, antioxidation, appetite loss, and thermogenesis.The efficacy was evident in regulating lipid parameters, cytokines, hormones, or genes.By comprehensively understanding the efficacy and related mechanisms, this review extensively identified the potential effects of various natural products for treating obesity.

Anti-Inflammation
Twenty-one natural products modulated the inflammation pathway, and twenty studies explained their mechanisms (Figure 3).

Antioxidant
The next mechanism associated with antiobesity is antioxidation (Figure 4).Ten studies noted antioxidant effects, but only two discussed the antioxidant mechanism associated with their compound's significant efficacy.

Appetite Loss
Twelve studies established a connection between appetite and the effects of natural products, and nine mentioned the mechanism underlying this effect (Figure 5).Among the three excluded studies, one did not show a significant appetite suppression effect but reported a related mechanism.Appetite loss manifests as increased anorexigenic factors and decreased orexigenic factors.High oxidative stress and free radicals increase AChE activity.However, A. melanocarpa decreased the AChE activity in the erythrocyte membranes [46].Superoxide dismutase (SOD) catalyzes the dismutation of the superoxide anion to H 2 O 2 , then catalase (CAT) and glutathione peroxidase (GSH-Px) degrade H 2 O 2 .GSH-Px also oxidizes reduced glutathione (GSH) to oxidized glutathione (GSSG), and GSSG is reduced to GSH by glutathione reductase (GR).A high-GO supplement elevated erythrocyte SOD, GSH-Px, and GR activities and lowered H 2 O 2 levels [50].Thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation caused by oxidative injury, were also reduced by the high-GO supplement [50].

Appetite Loss
Twelve studies established a connection between appetite and the effects of natural products, and nine mentioned the mechanism underlying this effect (Figure 5).Among the three excluded studies, one did not show a significant appetite suppression effect but reported a related mechanism.Appetite loss manifests as increased anorexigenic factors and decreased orexigenic factors.Ghrelin was lowered by A. melanocarpa extract, BPE-C, and LC-HS [46,48,62].LC-HS increased glucagon-like peptide-1 (GLP-1), an anorexigenic incretin produced by the intestinal L-cells that stimulates insulin secretion and induces satiety [18,62].Ghrelin was lowered by A. melanocarpa extract, BPE-C, and LC-HS [46,48,62].LC-HS increased glucagon-like peptide-1 (GLP-1), an anorexigenic incretin produced by the intestinal L-cells that stimulates insulin secretion and induces satiety [18,62].Ashwagandha root extract reduced stress, restoring leptin levels, which suppresses food intake [56].CAE phytochemicals, including limonene, γ-terpinene, trans-carveol, carvone, thymol, and carvacrol, improved the gastrointestinal microbiome to alter appetite [12].The phenylalanine content of S. platensis powder may be responsible for cholecystokinin release, which affects the brain's appetite center [54].The ephedrine and caffeine in Gambisan reversed obesity by reducing food intake via the sympathetic nervous system [67].

Thermogenesis
Ten studies mentioned the relationship between thermogenesis and the effects of natural products, though one only stated the effects without explaining the mechanism (Figure 6).Increased thermogenic gene expression and factors caused the browning of white adipose tissues.A carob-and wakame-enriched snack, melinjo seed, OPE, PGE, and GCBE induce uncoupling protein-1 (UCP1) in brown adipose [13,20,22,23,40].ASE increase uncoupling protein-2 (UCP2) expression, increasing energy expenditure an consumption [57].The sympathetic nervous system was considered related to energ expenditure through thermogenesis.Matured hop and Gambisan were believed t activate the nerve system [19,67].PGE increased the expression of thermogenic-relate genes, such as SIRT1, PPARα, and PGC-1α [23].Folate and hazelnut oil capsules lowere ADRB3 gene methylation levels [72].The ADRB3 protein facilitates the catecholamine induced activation of adenylate cyclase through the actions of G proteins.Thes mechanisms are involved in energy homeostasis by mediating thermogenesis.

Limitations
However, these studies had limitations.Some lacked information or wer unconvincing.The study about DEA was conducted for a short period with few participants, so its results have low reliability [8].Moreover, its study design was neithe blind nor placebo-controlled.Further studies on a larger scale and with a longe observation period are needed to support their conclusions.In addition, several studie A carob-and wakame-enriched snack, melinjo seed, OPE, PGE, and GCBE induced uncoupling protein-1 (UCP1) in brown adipose [13,20,22,23,40].ASE increased uncoupling protein-2 (UCP2) expression, increasing energy expenditure and consumption [57].The sympathetic nervous system was considered related to energy expenditure through thermogenesis.Matured hop and Gambisan were believed to activate the nerve system [19,67].PGE increased the expression of thermogenic-related genes, such as SIRT1, PPARα, and PGC-1α [23].Folate and hazelnut oil capsules lowered ADRB3 gene methylation levels [72].The ADRB3 protein facilitates the catecholamine-induced activation of adenylate cyclase through the actions of G proteins.These mechanisms are involved in energy homeostasis by mediating thermogenesis.

Limitations
However, these studies had limitations.Some lacked information or were unconvincing.The study about DEA was conducted for a short period with few participants, so its results have low reliability [8].Moreover, its study design was neither blind nor placebocontrolled.Further studies on a larger scale and with a longer observation period are needed to support their conclusions.In addition, several studies had many nonsignificant results, making it difficult to prove the efficacy of their natural products.Laboratory tests were left blank in the table when the obesity indicators were nonsignificant, the parameters were unrelated to obesity or lipid metabolism, or there were no serological indicators.Moreover, a few studies were the first clinical trials on their target compound [9,23,53,57,58,68,70,72].Therefore, the drug dosage was determined based on the results of animal experiments since there were no human reference data, leading to relatively low confidence in their experimental results.Finally, some studies focused on obesity-related bioavailability, such as metabolic disorders, inflammatory status, or antioxidant capacity, rather than on obesity itself.The effects of IP-A and IP-B were mainly studied on postprandial blood glucose and peak insulin, and the outcome for obesity was just peripheral [66].
This review also had some limitations that should be addressed in future studies.First, it only selected clinical trials, excluding in vitro and in vivo studies.In addition, it only included studies written in English.Lastly, while it contained natural products of various origins, reviews on each referenced study were insufficient.

Well-Designed Studies in Antiobesity
Despite these shortcomings, this review included specific mechanisms of obesity and its treatments, specific features of obesity, and laboratory test results that decreased obesity.Among the clinical trials analyzed in this review, three with outstanding results are especially noted below.First, the effects of GCBE combined with an energy-restricted diet on lipid composition were examined in 64 women with obesity aged 20-45 years [40].After eight weeks of taking 400 mg of GCBE, the intervention group showed significantly decreased BW, BMI, FMI, and WHR compared to the placebo group.These outcomes were supported by decreased serum TC, LDL, leptin, and FFA.In addition, this study investigated the change in serum APN levels with GCBE for the first time, showing they significantly increased in the experimental group.
Second, a mixture of grape pomace and omija fruit ethanol extracts was prepared to evaluate its effects on lipid profiles, inflammatory status, and antioxidant capacity [51].The dose-dependent antiobesity effect was outstanding.This combination was examined in three different groups: high-dose GO (grape pomace extract (685 mg/day) + omija fruit extract (115 mg/day); n = 26), low-dose GO (grape pomace extract (342.5 mg/day) + omija fruit extract (57.5 mg/day); n = 26), and control (starch (4 g/day); n = 24).GO was provided in capsules, and participants were encouraged to take two capsules twice daily for 10 weeks.The high-dose GO supplement reduced TC, non-HDL-C, LDL-C, plasma ApoB, and plasma Lp(a) and increased ApoA-1.This study demonstrated that GO could be an advantageous natural product for improving dyslipidemia and metabolic disorders in individuals with overweight or obesity without side effects.It also served as a meaningful preliminary study to determine the GO dose.
Lastly, Meratrim is a mixture of extracts from S. indicus flower heads and mangosteen fruit rinds [66].This study was a follow-up to evaluate the efficacy and tolerability of Meratrim, which was already proven effective against obesity in the previous study.Fiftyseven subjects were analyzed after taking a 400 mg Meratrim supplement twice daily for 16 weeks while consuming approximately 2000 kcal and walking 30 min daily for five days per week.Meratrim caused remarkable decreases in TG, LDL, and TC and increased glycerol production, AMPK, ACC phosphorylation, and HDL.The changes in these serological indicators led to reduced BW, BMI, and waist and hip size compared to the placebo group.Altogether, these findings indicate that this herbal formulation is effective and well tolerated in weight management in healthy individuals with overweight.Moreover, there were no adverse side effects.
It is evident that various studies have examined the effects of natural products on obesity.This review detailed the potential for the widespread use of natural products in treating obesity, which has not been reported in previous reviews on the same topic.Based on this review, further studies on safety, tolerability, and pharmacokinetics can be performed on these natural products to confirm their potential effectiveness.

Conclusions
This review comprehensively considered the effects of natural products against obesity by classifying sixty-two studies into various antiobesity mechanisms.Natural compounds, foods, tea, fruit, extracts, decoctions, and external preparations were found to show efficacy in lipid metabolism, anti-inflammation, antioxidation, appetite loss, and thermogenesis.Most studies showed positive effects in relieving the symptoms of obesity and demonstrated that natural products could be used as effective treatments for obesity.Therefore, herbal medicines are expected to be fully utilized in clinical obesity treatment.However, limitations remain in that some studies did not investigate efficacy or safety, and their nonsignificant results could be changed with precise control of drug dosages.Therefore, meta-analyses are needed to further examine their findings.Further studies are expected to refine the pharmacological effects of natural products for clinical use.

Figure 4 .
Figure 4. High oxidative stress and free radicals increase AChE activity.However, A. melanocarpa decreased the AChE activity in the erythrocyte membranes[46].Superoxide dismutase (SOD) catalyzes the dismutation of the superoxide anion to H2O2, then catalase (CAT) and glutathione peroxidase (GSH-Px) degrade H2O2.GSH-Px also oxidizes reduced glutathione (GSH) to oxidized glutathione (GSSG), and GSSG is reduced to GSH by glutathione reductase (GR).A high-GO supplement elevated erythrocyte SOD, GSH-Px, and GR activities and lowered H2O2 levels[50].Thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation caused by oxidative injury, were also reduced by the high-GO supplement[50].

Figure 4 .
Figure 4. High oxidative stress and free radicals increase AChE activity.However, A. melanocarpa decreased the AChE activity in the erythrocyte membranes[46].Superoxide dismutase (SOD) catalyzes the dismutation of the superoxide anion to H 2 O 2 , then catalase (CAT) and glutathione peroxidase (GSH-Px) degrade H 2 O 2 .GSH-Px also oxidizes reduced glutathione (GSH) to oxidized glutathione (GSSG), and GSSG is reduced to GSH by glutathione reductase (GR).A high-GO supplement elevated erythrocyte SOD, GSH-Px, and GR activities and lowered H 2 O 2 levels[50].Thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation caused by oxidative injury, were also reduced by the high-GO supplement[50].
IP-A and IP-BIP-A: A mixture of Morus alba (white mulberry),