applied sciences

Review Natural Dietary and Medicinal with Anti-Obesity Therapeutics Activities for Treatment and Prevention of Obesity during Lock Down and in Post-COVID-19 Era

Wenli Sun 1,*,†, Mohamad Hesam Shahrajabian 1,*,† and Qi Cheng 2,3

1 Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China 2 State Key Laboratory of North China Crop Improvement and Regulation, Hebei Agricultural University, Baoding 071000, China; [email protected] 3 Global Alliance of HeBAU-CLS&HeQiS for BioAl-Manufacturing, College of Life Sciences, Hebei Agricultural University, Baoding 071000, China * Correspondence: [email protected] (W.S.); [email protected] (M.H.S.); Tel.: +86-13-4260-83836 (W.S.) † Authors contributed equally to this research.

Abstract: Overweight and obesity have become global epidemics, especially during the lockdown due to the COVID-19 pandemic. The potential of as a better and safe option in treating obesity and overweight has gained attention in recent years. Obesity and overweight has become a major public health concern, and its incidence rising at an alarming rate. Obesity is one of the major types of metabolic syndrome, resulting in various types of problems such as hypertension,   , dyslipidemia, and excess fat accumulation. The current searching was done by the keywords in main indexing systems including Scopus, PubMed/MEDLINE, the search engine of Google Scholar, Citation: Sun, W.; Shahrajabian, and Institute for Scientific Web of Science. The keywords were , health benefits, M.H.; Cheng, Q. Natural Dietary and Medicinal Plants with Anti-Obesity pharmaceutical science, pomegranate, punicalin, punicalagin, and ellagitannins. Google Scholar Therapeutics Activities for Treatment was searched manually for possible missing manuscripts, and there was no language restriction and Prevention of Obesity during in the search. This review was carried out to highlight the importance of medicinal plants which Lock Down and in Post-COVID-19 are common in traditional medicinal sciences of different countries, especially Asia to prevent and Era. Appl. Sci. 2021, 11, 7889. treatment of obesity and overweight during the global pandemic and the post-COVID-19 era. https://doi.org/10.3390/ app11177889 Keywords: COVID-19; obesity; natural products; medicinal plants; overweight; body mass index; global pandemic Academic Editor: Martin C. Gruhlke

Received: 20 July 2021 Accepted: 17 August 2021 1. Introduction Published: 26 August 2021 Traditional medicine is used not only for treatment but also for prevention [1–6],

Publisher’s Note: MDPI stays neutral which is as old as mankind itself [7]. Medicinal plants which have been used in traditional with regard to jurisdictional claims in medicinal science have relatively minimum or no negative impacts and toxicity, and their published maps and institutional affil- applications have been increased because of accessibility, affordability, easy availability, iations. and acceptable efficacy [8–10]. Obesity is the main and primary reason of various metabolic ailments according to the epidemiological evidence, such as hypertension, diabetes, car- diovascular complications [11,12], asthma, arthritis, non-alcoholic fatty liver, degenerative disease, etc. [13]. Obesity is a serious health issue causing numerous health impairments, such as musculoskeletal disorders, cardiovascular diseases, type-2 diabetes, and different Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. types of cancer [14]. Vulnerability to COVID-19 increases due to obesity, because both This article is an open access article diseases share common inflammatory/metabolic pathways [15]. Notable changes in diet, distributed under the terms and sleep, physical activity, and mental health were reported by participants during the lock- conditions of the Creative Commons down [16]. The Centers for Disease Control and Prevention list severe obesity (body mass 2 Attribution (CC BY) license (https:// index of ≥40 kg/m ) as a risk parameter for severe illness from COVID-19 [17]. During the creativecommons.org/licenses/by/ pandemic, promotion of physical activity and prevention of obesity are as important as 4.0/). physical isolation of severely obese individuals [18]. Physical activity, maternal prenatal

Appl. Sci. 2021, 11, 7889. https://doi.org/10.3390/app11177889 https://www.mdpi.com/journal/applsci Appl. Sci. 2021, 11, 7889 2 of 23

diet, psychological stress, sleep quality, and oxidative stress promoting disease conditions are important modulators of obesity and oxidative stress [19,20]. Obesity in individuals with COVID-19 independently has a relationship with increased risk for ICU admission and intubation [21,22]. Fat accumulation is caused by low levels of daily exercise and excessive food intake, which may influence fatty acid synthesis and betaoxidation. A linear dose–response link between body mass index and COVID-19 severity and mortality has been suggested, and obesity (body mass index ≥ 30 kg/m2) may cause a significantly increase in risk of critical COVID-19 and in-hospital mortality of COVID-19 [23,24]. Natural sources provide an advantageous basis for development of novel anti-obesity products [25]. Food supplements and functional foods containing fruit extracts, vegetables, and products are also gaining increased attention [26] as an important natural alternative to prevent metabolic syndrome and obesity [27,28]. This review article is aimed to introduce and survey the most important medicinal plants on the basis of different traditional medic- inal sciences containing chemical constituents with anti-obesity activities for treatment and prevention of obesity and related disease during the pandemic, quarantine, and the post-COVID-19 era.

2. Materials and Methods The manuscript covers review articles, randomized control experiments, analytical studies and observations, which have been gathered from different sources such as Google Scholar, Scopus, Science Direct and PubMed. A review of the literature was carried out using the keywords COVID-19, obesity, natural products, medicinal plants, overweight, body mass index, and global pandemic.

3. Obesity It has been reported that nutritional management may have obvious effects on the risk for chronic and obesity diseases [29,30]. The measurement tool which is mainly used in the clinical studies to identify obesity and overweight is called body mass index (BMI), which classifies people as normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2)[31–33]. Obesity affects mortality, morbidity, and quality of life [34]; moreover, both overweight and obesity have increased attention in different societies, especially in urbanized populations [35,36]. Obesity shows harmful impacts and is believed to contribute to the increasing cardiovascular mortality [37]. Being overweight or obese is a risk factor for various costly comorbidities, such as type 2 diabetes (T2D), sleep apnea, chronic pain, cardiovascular disease, and certain cancers [38,39]. The frequency of obesity and overweight among children is increasing in the European region [40] and Canada [41], and women are presently more likely than before to suffer from obesity problems [42]. Impaired glucose tolerance of obese children is believed to exhibiting emerging oxidative stress levels [43]; obesity of childhood is a big concern as it is a principal predictor of obesity in adulthood [44]. The link between the presence of risk factors for different diseases and obesity in childhood with the early development of those diseases has been proven [45]. Prevention as well as treatment of obesity is important for children [46]. Obesity is linked with consequences of pneumonia, a protective impact coined the obesity paradox [47]. Obesity rates have dramatically risen among patients needing rehabilitation following join arthroplasty, injury, stroke, or an acute medical event [48]. Obesity may increase the risk of cardiovascular disease [49], and it is a risk factor for asthma [50].Obesity influences female reproduction by disturbing the hormone metabolism, the follicular environment, and body metabolism [51]. There is also a connection between obesity and cognitive reactivity, as well as depression [52]. An important risk factor for obesity is sleep duration [53]. The relationship between periodontal risk indicators and obesity in adolescents which may lead to oral morbidity has been found [54]. The important symptoms of metabolically healthy or unhealthy parameters are waist circumference, low-grade inflammation, HDL cholesterol, blood pressure, and diabetes [55]. Appl. Sci. 2021, 11, 7889 3 of 23

4. Obesity and COVID-19 The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has spread quickly from Wuhan, China to all parts of the world. A significant increase rate of obesity was found during the era of the COVID-19 epidemic [56,57], and also among obese patients with obstructive sleep apnea (OSA), an increased prevalence of COVID-19 was reported [58]. COVID-19 may lead to economic shutdown, confinement, and direct impacts, and conse- quently obesity development and eventually increased susceptibility to COVID-19 [59–61]. The worse outcomes of obese patients with COVID-19 consist of need for mechanical ventilation which is the consequence of respiratory failure and increase number of mor- talities [62]. Body mass index, weight, and overweight escalated among children during the COVID-19 lockdown, influencing disadvantaged subpopulations, and related methods are required to decrease the impacts of the COVID-19 lockdown on childhood obesity and unhealthy weight gain [63]. The higher body mass index (BMI) in COVID-19 patients was reported, which is an important parameter that should always be evaluated for treatment and management of COVID-19 patients [64]. Obesity significantly increases the risk for hospitalization, demanding intensive care unit (ICU) admission, needing invasive mechan- ical ventilation (IMV) support, and risk for death among patients with COVID-19 [65–67]. Reports from the USA and Europe revealed remarkable morbidity and mortality in obese individuals with COVID-19 [68]. Obesity may have a noticeable role in the high incidence of mortality in black and Hispanic populations [69]. Recognition of populations with high fatality in COVID-19 gives clear insight to manage the pandemic by health services [70]. A need for policies is suggested which may support healthy lifestyle behaviors among low-income children during the pandemic [71]. Obesity may contribute to the increased risk and poorer prognosis of COVID-19 [72]. Obesity has a relationship with an immune state favorable to a cytokine storm, and serum concentrations of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-17A are more increased in patients with obesity and COVID-19, and finally, they have a greater possibility of developing acute respiratory dis- tress syndrome (ARDS) and death [73]. Biopsychosocial parameters which may influence COVID-19 pandemic-related obesity in children are (a) biological parameters including acute stress effects, altered leptin and adiponectin, chronic inflammation, intestinal dysbio- sis, dysregulated immunological response, and stress increased inflammation and immune response; (b) social parameters such as household size, food insecurity, increased caloric consumption, increased screen time, lower educational achievement, parental factors, social distancing, sedentary lifestyle, socioeconomic status, and unhealthy diet; (c) psychological parameters like boredom, anxiety, food attitudes, food behavior, irritability, lack of self- regulation, maternal mental health loneliness, sleep disorders, and mental distress [74]. Reduced antithrombin is connected to mortality in COVID-19, and it has a relationship with obesity in COVID-19 [75–77]. Obesity and type 2 diabetes may have a role in the severity of disease and even mortality [78]. Subjects with obesity influenced by COVID-19 need longer hospitalization and much more time to clear from COVID-19 shedding com- pared to patients without obesity [79]. Inappropriate immune response is generated by obesity-induced chronic inflammatory status [80]. Isolation and quarantine can induce anger, anxiety, depression, and stress which are associated with unhealthy lifestyle leading to obesity. Higher BMI is connected with lower diet quality and levels of physical activity and a greater reported frequency of overeating during the lockdown [81]. Obesity could alter severe COVID-19 disease to younger ages [82]. Higher body mass index (BMI) and obesity are the major leading comorbidities to boost the risk of COVID-19 severity [83,84]. Obesity (BMI > 30 kg/m2) was connected with a significantly increased risk of critical COVID-19 and mortality [85]. Excess body weight multipliesthe risk of serious events connected to COVID-19 by 5.6 [86]. Dose–response meta-analysis indicates an increase of 5% risk for poor outcomes for every 5 kg/mg2 increase in body mass index [87]. There is a linear increase in risk of severe COVID-19 at a BMI of more than 23 kg/m2, leading to admission to hospital and death, and also a linear increase in admission to an ICU across Appl. Sci. 2021, 11, 7889 4 of 23

the whole BMI range was reported [88]. Obese patients needed longer hospital stay and more days of mechanical ventilation compared to non-obese patients [89].

5. Medicinal Plants and Obesity The increasing risk of obesity is associated with unhealthy foods [90,91], and consumption of healthy plant foods may be appropriate to decrease inflammation fac- tors like TGF-β and hs-CRP [92], and plants which may show great potency to prevent obesity may have significant potential to inhibit pancreatice lipase [93]. The negative relationship between water hardness in water purification plants and the percentage of obese people has been reported [94], while the effective intervention within a complex system approach to manage obesity may be formed by plant secondary metabolites [95]. with anti-obesity impacts are phenolic acids (o-Coumaric acid, Caffeic acid, Chlorogenic acid), Curcuminoids (Curcumin), Lignans (Podophyllotoxin), Flavonols (Quercetin), Isoflavonoids (Genistein, Daidzein, Glycitein), Flavones (Apigenin, Luteolin, Tangeritin), Flavans-3-ol (Catechin), Phytosterols (Diosgenin, Brassicasterol, β-Sitosterol, Campesterol), Anthocyanins (Cyanidin, Delphinidin, Malvidin, Pelargonidin, Peonidin), and Alkaloids (Caffeine, Capsaicin) [96]. Wheat (Triticum aestivum) sprout (TAEE) mean- ingfully reduced serum total cholesterol (TC), body weight, and low-density lipoprotein cholesterol levels in highfatdiet (HFD)-fed mice, and decreased lipid accumulation in epididymal white adipose tissue (EWAT) and liver. TAEE-treated mice indicated signif- icant reduction in peroxisome proliferator-activated receptor γ (PPARγ) and fatty acid synthase expression in EWAT, which proved its efficacy for therapy for obesity and related diseases [97]. It has been found that luteolin, which is a Chinese herb, may be putative Furin inhibitor with tremendous benefits against Dengue Fever, and application of Chinese and ion channel inhibitors can restrict the endothelial penetration of SARS-CoV- 2 [98]. Natural phenolic compounds can be beneficially applied as food or fortified foods to control obesity [99]. Wild edible from Southern Italy such as Daucus carota L., followed by Bel- lis perennis L. and Asparagusofficinalis L. showed inhibitory activity on NO production and protein denaturation, and D. carota indicated the best lipase inhibitory potential, which represented them as the appropriate candidates and the potential therapeutic agents in the treatment of obesity and inflammatory disorders [100]. Rosmarinus officinalis and Prunus avium contain the highest amounts of gallic acid, quercetin, ferulic acid, and epi- gallocatechin gallate which can be utilized against obesity in Turkish folk medicine [101]. The impacts of gut microbiota on obesity have been discovered in most animal and some human trials, and certain strains of Bacteroidetes, Firmicutes, and Lactobacillus have anti- obesity activities [102]. Apple, berries, chili, grapes, , sorghum, soy, and barley show anti-obesity efficacy via improving the diversity of gut microbiota, down-regulating obesogenic gut microbiota, and up-regulating anti-obesity gut microbiota [102]. Plant- based bio-active and fiber-enriched diets help in the alleviation of obesity and related diseases [103]. The most famous traditional medicinal plants in India for treatment of diabetes mellitus ailments, and potent candidates and substitutes to synthetic drugs in obese models are Acalypha indica, Pergulari ademia, and Tinospora cardifolia [104]. Folk herbal medicines for obesity are Zingiber officinale Roscoe, Carica papaya L., Hibiscussabdariffa L., Bauhinia variegata L., Foeniculum vulgare Mill., Caralluma tuberculata N.E.BR., Prunus avium (L.), Citrus medica L., Senna alexandrina Mill., Rosmarinus officinalis L. [105,106], Fucus vesicu- losus, and Citrus aurantium [107]. In South Africa, three medicinal plants, namely Curtisia dentate, Cissaempelos capensis, and Schotia latifolia were repeatedly highlighted by the tradi- tional healers and the local dwellers to have weight-reducing properties [108]. In Brazil, some of the most important species with great effective anti-obesity properties are Annona muricata L. and Hancorniaspeciosa Gomes, Baccharis trimera (Less.) DC, Camellia sinensis (L.) Kuntze, and Hibiscus sabdariffa L., showing some beneficial activity against obesity [109]. A natural pigment that mainly exists in the mature fruit of tomatoes is called lycopene, which effectively contributes to protecting against obesity and diabetes in animal stud- Appl. Sci. 2021, 11, 7889 5 of 23

ies [110]. Wines and grape berries are reported as the principal sources of stilbenes in human nutrition, which can alleviate the adverse effect of obesity by regulating vari- ous pathways [111]. By-products of guava and acerola can be applied as a sustainable alternative in the treatment of obesity [112]. Rosmarinic acid prevents excessive lipid accumulation and inflammation in human adipocytes, which shows its great potency for treatment of obesity-related inflammation [113]. Garlic extract in combination with can prevent obesity in rats, and improved antioxidant enzyme’s activity [114]. A bioactive compound in celery (Apium graveolens) is 3-N-butylphthalide (NBP), which blocks the inflammatory response and regulates fat browning in HFD-induced obese mice, which indicates its effectiveness in combating obesity and its related metabolic disorders [115]. Various natural agents have been discovered for their obesity treatment potential such as Garcinia cambogia, apple cider, green tea, Panax , chia seeds, etc. [116]. Witha- nia somnifera Dunal presented blood glucose-lowering and impacts in humans, comparable to daonil [117]. Acia (Euterpe oleracea Mart.) fruit anthocyanins decreased high-fat diet-induced obesity and hepatic steatosis, and increased high-fat diet-induced insulin resistance [118]. One of the promising anti-obesity agents is coffee fruit and oneof the traditional Chinese medicines is Caffeic acid [119]. Berberine is found to have an effective influence on gene regulation for the absorption of cholesterol at a daily dose of 300 mg in humans [120]. A classic traditional Chinese herb medicine which is called Wu- Mei-Wan can prevent obesity and its underlying mechanisms through attenuating white adipose tissue and increasing brown adipose tissue function [121]. Isolated Tomatidine from the green fruits and of some plants in the Solanaceae family may significantly suppress the expression of fatty acid synthase and transcription factors are involved in lipogenesis and improve the expression of adipose triglyceride lipase, promoting the sir- tuin 1 (sirt1)/AMPK signaling pathway to boost lipolysis and β-oxidation in fatty liver cells [122]. Hibiscus (Hibiscus shizopetalous; Hibiscus subdariffa), Argel (Solenostemma argel), and Caralluma (Caralluma quadrangular; Caralluma tuberculata) are famous traditional medic- inal plants, and Argel indicated the highest inhibitory activity against lipase, α-amylase, and α-glucosidase enzymes, and the strongest lipase inhibitory activity was reported for the pregnane , and stemmoside C [123]. Roselle (Hibiscus sabdariffa) showed adipogenesis, reduced oxidative stress and systemic inflammation, and increased obesity- induced insulin resistance and insulin sensitivity [124]. EGCG, , and quercetin have shown significant potent capability of anti-obesity activities [125,126]. Grape seed flour (GSF) prevented diet-induced obesity in C57BL/6J mice [127]. Procyanidins are a group of flavonoids, showing anti-obesity effects and increased metabolic flexibility and energy expenditure [128]. Crataegus pubescens and Ocimum sanctum ameliorated obesity and hyperglycemia in obese rats, reduced adipocyte hypertrophy, and can be introduced as ingredients for the elaboration of functional beverages [129]. The saprophytic fungus belongs to the family polyporaceae, Poria cocos, and synthesized Poria cocos gold nanopar- ticles caused the distinctions of influential nanoparticles which proved its ability as the potent anti-obesity drug [130]. Hussein et al. [131] reported that green coffee bean aqueous extracts and Spirulina platensis reduced liver weight, the final body weight, and the serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphate, and they can be potentially considered as anti-obesity substances. Cercato et al. [132] also reported that the flavonoids quercetin, naringenin, genistein, epigallocatechin gallate, api- genin, and cyaniding 3-glucoside have potential in complementary therapy against obesity. Some of the most important plants, herbs, and fruits with anti-obesity characteristics are shown in Table1. Appl. Sci. 2021, 11, 7889 6 of 23

Table 1. Anti-obesity potential of some medicinal plants and fruits.

Plant Plant Family Key Point References Acosmium dasycarpum (Vog.) It is a Brazilian medicinal plant known as Yakovlev Fabaceae “Unha D/anta”, especially found in the [133] (Unha D/anta) Cerrado (Brazilian Savanna) area. Ascomium dasycarpum promoted metabolic syndrome; its root bark clearly ameliorates triglycerides; it has beneficial [133] impacts on adiposity and weight reduction. Onion peel extract meaningfully reduced the lipids of 3T3-L1 cells and restricted Allium cepa L. Amaryllidaceae lipid accumulation by decreasing the [134] (Onion) expression of lipogenesis-related genes, with impressive anti-obesity impacts. barbadensis Miller Aloe vera application regulated [135] (Aloe vera) adipose tissue accumulation in obese rats. Aloe vera gel regulated the dyslipidemia [135] as well as oxidative stress in obese rats. It has positive impacts on prevention and Amorphophallus konjac K. Koch Araceae treatment of obesity because of its [136] (Konjac) components konjak and glucomannan. Artemisia sphaerocephala Its polysaccharide fractions Krasch Asteraceae [137,138] prevent obesity. (Artemisia) Betula utilis bark is rich in pentacyclic Betula utilis triterpenoids thus it can be considered for Betulaceae [139] (Himalayan birch) management of overweight and associated comorbidities. Bupleuri Radix extract (BupE) increased Bupleuri Radix Apiaceae HFD-induced lipid disorders through [140] (Chaihu) FGF21 signaling pathway. BupE reversed obesity-related changes in structure and function of gut [140] microbial communities. Butea monosperma Its flower extract can normalize the Fabaceae [141] (Sacred Tree) weight gain parameters. Application with C. fimbriata extract while controlling overall dietary intake Caralluma fimbriata Apocynaceae and physical activity may be useful in [142] curbing central obesity, and the key component of metabolic syndrome. Molokhia extract ameliorated guy Corchorus olitorius L. Malvaceae dysbiosis and high-fat [143] (Nalta jute) diet-induced obesity. It contains essential fatty acids, flavonoids, volatile oils, etc., and may Cuminum cyminum L. Apiaceae have influence on weight and other [144] (Cumin) anthropometric indices in obese and overweight people. Cumin promoted anthropometric and Carum carvi L. Apiaceae metabolic indices in overweight and type [145,146] () 2 diabetic subjects. Appl. Sci. 2021, 11, 7889 7 of 23

Table 1. Cont.

Plant Plant Family Key Point References As a traditional medicine, it may attenuate body mass index, body fat [147] percentage, and body weight loss. It has been used as the Cyclopia spp. (honeybush), which shows anti-obesity Fabaceae [148] (Honeybush) effects, especially by targeting adipose tissue. Cynara scolymus L. Artichoke has tremendous potency as Asteraceae [149] (Artichoke) anti-obese agent. Cynometra cauliflora Linn. Fabaceae It can be used for obesity management. [150] (Nam-nam) HCY2, a triterpenoid-enriched extract of Cynomorium songaricum Rupr. Cynomoriaceae Cynomorri Herba treat obesity via the [151] (Suo Yang) regulation of AMPK/PGC1 pathways. It can be considered as the potent Echium angustifolium Mill. Boraginaceae candidate for oxidative stress, diabetes, [152] and obesity. OBE100 and OBE104 are natural Eu extracts which are rich in pentacyclic triterpenes, and can be used to combat [153] obesity and diabetes, and treatment with OBE100 had better effects than OBE104. Garcinia cambogia and Glucomannan Garcinia cambogia decrease weight, alter body composition, Clusiaceae [154] (Garcinia) regulate lipid and glucose blood profiles in overweight/obese patients. It may reduce the body weight, organ weights, anthropometric indices, Gnidia glauca (Fres.) Gilg Thymelaeaceae organo-somatic indices, the total fat [155] (Fish Posion Bush) content, adiposity index, atherogenic index, and various lipid profiles. Ganoderma lucidum sensu stricto Ganodermataceae It has shown anti-obesity effects. [155,156] (Mushroom of immortality) Cholesterol and triglycerides levels Hibiscus sabdariffa L. indicated non-significant reductions in Malvaceae [157] (Roselle) animals treated with Hibiscus sabdariffa, with its anti-obesity effect. After treatment with Ilex paraguariensis, a Ilex paraguariensis drop in respiratory quotient (RQ) was Aquifoliaceae [158] (Yerba mate) observed, revealing a rise in the proportion of fat oxidized. The methanolic leaf extract of Justicia carnea is a rich natural source of Justicia carnea Lindl. Acanthaceae antioxidant and anti-obesity agents [159] (The Brazilian plume flower) which could be optimized for development of new anti-obesity drugs. It is an indigenous plant with significant Juniperus communis L. Cupressaceae in vitro anti-obesity impacts in [160] (Common Juniper) adipocytes differentiation. Appl. Sci. 2021, 11, 7889 8 of 23

Table 1. Cont.

Plant Plant Family Key Point References In Chinese folk medicine, its leaves are used in the treatment of obesity and Ligustrum robustum Blume Oleaceae hyperlipidemia, and its anti-obesity [161] impact was associated with up-regulation of leptin. Polysaccharide from Lobelia chinensis lour Lobelia chinensis lour is an insulin-type fructan with Mw of 2.6 Campanulaceae [162] (Asian lobelia) kDa that indicated the potential of anti-obesity effect in HFD-induced mice. Macrotyloma uniflurom formulation may increase the activity of enzymatic Macrotyloma uniflorum (Lam.) superoxide dismutase, glutathione Verdc. Fabaceae peroxidase, catalase, and non-enzymatic [163] (Horse gram) antioxidants and could be applied in treatment and prevention of fat-induced oxidative stress and inflammation. Its anti-obesity activity may be mediated partially via pancreatic lipase inhibitory Mangifera indica Linn. Anacardiaceae activity and partially through reduction [164] (Mango) in food intake and improvement of antioxidant status. The herbal extract ALS-L1023 may block visceral obesity, and also decreases the Melissa officinalis L. Labiatae increased fasting blood glucose, impaired [165] () glucose tolerance, and pancreatic dysfunction seen in female obese mice. The oral administration of methanolic extract in mice may decrease Memecylon umbellatum Burm. f. Melastomataceae hyperglycemia, triglycerides, body [166] (Ironwood) weight, and ameliorates insulin resistance. Its extract up-regulated adiponectin gene Moringa oleifera Lam. expression in obese rats relative, and Moringaceae [167] (Drumstick tree) down-regulated mRNA expression of leptin and resistin. Traditionally, M. oleifera leaves considered as anti-obesity [168] . Its oil extract is considered to have cholesterol-lowering properties and a [169] potential to treat obesity, while lycopene is a potent antioxidant. Its bark and leaf extracts revealed potential anti-obesity and Moringa peregrine (Forssk.) hepatoprotective activity through Moringaceae [170] Fiori. reduced lipid absorption, anti-hyperlipidemic impacts, and hepatic antioxidant effects. The inhibitory impacts of mulberry on digestive enzymes and adipocyte Morus alba L. differentiation, and its stimulatory Moraceae [171] (Common mulberry) influences on energy expenditures, and lipid metabolism may have a role in obesity regulation. Appl. Sci. 2021, 11, 7889 9 of 23

Table 1. Cont.

Plant Plant Family Key Point References Nigella sativa L. It shows a moderate impact on reduction Ranunculaceae [172] ( flower) in body mass index and body weight. Oroxylin A, chrysin and baicalein were Oroxylum indicum (L.) Kurz Bignoniaceae suppressed lipid accumulation in 3T3-L1 [173] (Kyaung shar) preadipocytes and PL enzyme. Oroxylin A and chrysin also suppressed PPARγ and C/EBPα, main adipogenic transcription factors, in 3T3L-1 [173] preadipocytes during adipogenesis process at 50 µM dose. Passiflora edulis peel flour could be Passiflora edulis Sims Passifloraceae considered as an adjuvant to control of [174] (Passion fruit) early parameters in obesity dysfunction. Its stem extract enhanced serum lipid profile of the animals, lessened Pilosocereus gounellei (F.A.C. Cactus atherogenic indices, liver steatosis, [175] Weber) Byles and G.D. Rowley epididymal fat, and pro-inflammatory cytokines. Piperine was separated from methanolic extract of Piper nigrum seeds, which may Piper nigrum L. Piperaceae have suppressed role in body weight, [176] (Black pepper) increase insulin and leptin sensitivity, ultimately leading to balance obesity. It has been known as a culturally adapted Populus balsamifera L. Salicaceae therapeutic approach for the treatment [177] (Balsam poplar) and care of diabetes and obesity. Guava leaves promoted the vascular Psidium guajava L. dysfunction in obese mice, and its Myrtaceae [178] (Common guava) application may have a positive effect on metabolic functions in obese mice. It is generally regarded that Saptrangi and Salacia chinensis-loaded gold Salacia chinensis L. nanoparticles ameliorate body weight, Celastraceae [179] (Chinese salacia) adipose index, resistin, inflammatory markers and AMPKα1, liver marker enzymes, leptin, and lipid profile. Chia oil increased glucose metabolism Salvia hispanica L. and it has revealed potential to protect Lamiaceae [180] (Chia) against the development of obesity-related diseases. Salvia officinalis L. Common sage provides novel natural Lamiaceae [181] (Common sage) treatments for the relief or cure of obesity. Smilax china L. polyphenols may be Smilax china L. Smilaceae applied as a potential candidate to [182] (Baqia) prevent obesity. Smilax glabra rhizome may change the Smilax glabra Roxb. Smilaceae anti-obesity constraints in high-fat diet [183] (Glabrous greenbrier) and obese diabetes in animal models. Argel is a promising Egyptian natural Solenostemma argel Hayne Apocynaceae substitute, as it is rich in [184] pregnane . Appl. Sci. 2021, 11, 7889 10 of 23

Table 1. Cont.

Plant Plant Family Key Point References The n-BuOH extract of Taheebo TabebuiaavellanedaeLorentz ex prohibited ovariectomy-induced obesity Bignoniaceae [185] Griseb and reduce fat mass in ovariectomized mice. It was discovered to be efficacious in Tinospora cordifolia (Thunb.) regulating body weight in a high-fat diet Menispermaceae [186,187] Miers. (HFD)-fed rats by keeping energy metabolism and cellular homeostasis. Urtica dioica L. It may decrease diet-induced weight gain Urticaceae [188] (Common nettle) and insulin resistance. Vaccinium arctostaphylos berry may have antihypertensive influence, and Vaccinium arctostaphylos L. Ericaceae significantly lowers systolic and diastolic [189] (Caucasian whortleberry) blood pressures in overweight/obese hypertensive patients. Withaferin A (WFA) which is the principal component of Withania Withania somnifera (L.) Dunal somnifera extract, restricted HFD-induced (Winter cherry or poison Solanaceae obesity, and regulated mitogen-activated [190] gooseberry) protein kinase (MAPK) signaling and AMP-activated protein kinase (AMPK) in adipose tissue.

Two famous traditional Chinese medicines, namely Rheum palmatum L. (Chinese rhubarb) (Polygonaceae), and Prunella vulgaris L. (the common self-heal) (Labiatae) are rich sources of anti-lipase compounds which can be considered as natural sources for crude anti-obesity drugs [191]. Consumption of bitter almond gum may decrease body mass index and body weight, alleviate hyperinsulinemia in hyper lipidemic subjects, re- duce serum triglycerides, and can be applied for the management of body weight in fruit juices [192]. Saponins are the best candidate as appetite suppressants and pancreatice lipase, and may manage fattlier liver formation and body weight [193]. Acacia arabica, Agri- monia eupatoria, Aegle marmelose, Allium sativum, Allium cepa, , Aloe vera, Beta vulgaris, Benincasa hispida, Caesalpinia bonducella, Coccinia indica, Citrullus colocynthis, Eucalyptus globules, Ficus bengalenesis, Gymnema sylvestre, Hibiscus rosasinesis, Ipomoea batatas, Jatropha curcus, Mangifera indica, Morus alba, Momordica charantia, Mucuna pruriens, Oci- mum sanctum, Punica granatum, Pterocarpus marsupium, Syzigium cumini, Tinospora cordifolia, and Trigonella foenum graecum are the most notable plants with antidiabetic potential in Indian traditional medicine with anti-obesity characteristics [194]. Dietary fruit intake was positively associated with P53 and PTEN gene expression in visceral and subcutaneous adipose tissues (SAT) obese participants [195]. Dandelion (Taraxacum officinale (L.)) and luteolin may improve HDLcholesterol in obese rats fed a normal-fat diet [196]. The natural compound celastrol, a pentacyclic triterpene isolated from the roots of Tripterygium wilfordi (thunder god vine) plant shows different bioactivities including and antidiabetic and anti- obese impacts [197]. The impacts of taking the combination of Zataria multiflora Boiss. (Zm) and oxymel may reduce insulin resistance and hip and wasit circumferences in overweight patients [198]. Dietary ginger controls body weight gain by inducing browning of white adi- pose tissue (WAT) and remodeling whole-body energy metabolism [199]. Coleus forskohlii extract and Garcinia indica extract increase energy expenditure through promotion of fatty acid β-oxidation, and attenuating the Firmicutes/Bacteroidetes to attenuate obesity [200]. African walnuts reduced lipid accumulation in adipose and ectopic tissues in MSG-obese rats [201]. Red maple (Acer rubrum) leaves extract decreased diet-induced obesity with- out influencing energy intake, and its impacts are partially because of the modulation of Appl. Sci. 2021, 11, 7889 11 of 23

gut flora [202]. Indian brown algae ( Padina tetrastromatica) is the major component for obesity management [203]. Fagara tessmannii is a shrub of the African rainforests in the South-West, Center, South, and East provinces in Cameroon, regulating the loss of ectopic fat and other fatty tissues, the energy expenditure and the renovascular decompression, the sensitivity of the peripheric tissues to insulin, and promotes ion movement which prevents hypertension [204]. The ethanolic extracts of Actaea racemosa L. have been proven as the best candidate for treatment of obesity and related diseases for further studies [205]. Garcinia indica extract standardized for 20% Garcinol inhibited adipogenesisin vitro3T3- L1 cells, decreased endoplasmic reticulum stress in adipocytes, alleviated visceral fat weight, and regulated obesity by acting on the AMPK-ER stress axis [206]. Chrysin is a flavonoid found in plant extracts from Passiflora species, alleviated the body weight of rats, decreased calorie intake of rats, and the hypertrophy of adipocytes [207]. Applica- tion of licorice extract with a low-calorie diet can efficiently increase the lipid profile in overweight and obese subjects [208]. The anti-obesity activities of the essential oils of hedgenettles (Stachys inflata, S. lavandulifolia, and S. byzantina) have been reported [209]. Huang-Qi San (HQS), the traditional Chinese medicine, can ameliorate hyperlipidemia with obesity [210]. Meratrim formulation, yerba mate, spinach, brown beans, sorghum, psyllium, and rye showed evidence for suppressing appetite [211]. A combination of resistance training with 500 mL/g of glycyrrhizic acid supplement may be appropriate to decrease body weight and body fat percentage [212]. In Mexico, one of the common herbal products used for weightloss is based on soybean, green tea, and aceitilla [213]. Methylxanthines are nutraceuticals mainly present in tea, coffee, and chocolate, and the most well-known methylxanthines are theophylline, caffeine, and theophylline, which can contribute to weight loss, fat depletion, and inhibit adipogenesis and stimulate lipoly- sis [214]. Berberine consumption significantly decreased body mass index and alleviates waist circumference (WC) [215]. Cooked mung bean may prevent obesity in mice fed with a highfatdiet and regulates lipid metabolic disorders [216]. Garlic oil had a significant anti-obesity influence on obese rats by protecting the liver from damage and regulating the body weight [217]. A significant decrease of intracellular lipid accumulation in 3T#-L1 pre-adipocyres, improvement of plasma lipid profile in HFD-induced mice, and regulation of body weight gain has been reported due to application of bound phenolics isolated from lotus seeds [218]. The ethanolic extract of Cuscuta reflexa suppressed the development of obesity in HFD-induced obesity [219]. Hunteria umbellate (K. Schum.) Hallier f. indi- cated both antihyperlipidaemic and anti-obesity effects which may partly be mediated via inhibition of intestinal lipid absorption and de novo biosynthesis of cholesterol [220]. Lagenaria siceraria (fruit) and Commiphora mukul (gum resin) can regulate the high fat diet- induced obesity [221]. Erigeron annuus L., and Borago officinalis L. significantly attenuated improved in body weight gain, lipid accumulation, and adipocyte size, a unique adipokine known to promote the breakdown of fat/lipids [222]. Blueberry had potential health benefits in ameliorating the development of obesity and its related comorbidities, such as chronic inflammation and type 2 diabetes [223]. Morin (3,5,7,2,4-pentahydroxy flavones) is found in some natural products such as almond (Prunus dutcis), figs (chlorophora tinctoria), guava leaves (psidium guajava), and some other Maraceae family plants [224,225]; morin treatment produced dose-dependent improvement in lipid profile and vascular endothe- lium protection, thus rationalizing its medicinal use in cardiovascular-related endothelial disorders, and dyslipidemia diseases [226]. In Kampo, Japanese traditional medicine, two formulas, this bofutsushosan (the composition of scutellaria root, platycodon root, gly- cyrrhiza, atractylodes rhizome, gypsum, rhubarb, schizonepeta spike, peony root, gardenia fruit, Japanese angelica root, cnidium rhizome, menthe herb, saposhnikovia root, forsythia fruit, Ephedra herb, ginger) and boiogito (the composition of astragalus root, sinome- nium stem, jujube, atractylodes lancea rhizome, glycyrrhiza, and ginger) are supported by the national health insurance in Japan for treatment of obesity [227]. In Bangladesh, the most important medicinal plants with anti-obesity characteristics are Achyranthes aspera Linn, Aegle marmelos Linn, Alliun sativum Linn, Acorus calamus Linn, Allium cepa Linn, Appl. Sci. 2021, 11, 7889 12 of 23

Bombax ceiba L., Moringa oliefera, Hibiscus sabdariffa L., Impomoea batatas L., Punica granatum L., Citrus limon L., and Zingiber officinale Roscoe [228]. One of the screening methods applied in the discovery of anti-obesity drugs is to search for potent lipase inhibitors from plant extracts; the major plant extracts that inhibit porcine pancreatic lipase (PPL) are Platycodon grandiflorum A. De Candolle, Aconitumcarmichaeli Debeaux, Chaenomeles sinensis (Thouin) Koehne, sativa Linne, Actinidachinensis, Tribulus terrestris, Luffa cylindrical Roemer, Lilium brownii var. viridulun Baker, Pueraria thunbergiana Bentham, Crataegus pin- natifidaBunge var. typical Schneider, Nardostachys chinensis Batal, Zizyphus jujuba Miller Var. inermis Rehder, Akebia quinata Decaisne, Quisqualis indica Linne, Rehmannia glutinosa, Loranthus parasticus Merr., Schizandra chinensis Baillon, Lonicera japonica Thunberg, Dip- sacus asperoides C. Y. Cheng et T. M. Ai, Perilla sikokiana Nakai, Morinda officinalis How, Prunus nakaii Leveille, Melia azedarachLinne var. japonica Makino, Poria cocos wolf, Gastro- dia Blume, Bletilla striata (Thunberg) Reichenbach fil., Oldenlandia diffusa (Willd.) Roxburgh, Gentiana scabra, Cuscuta chinensis Lamark, Tetrapanax papyriferus K. Koch, Fritillaria thun- bergii Miquel, Astragalus membranaceus Bunge, Patrinia villosa Jussieu, Scutellaria baicalenis Georgi, Phellodendron amurense Ruprecht, Rubus coreanus Miquel, Drynaria fortunei Smith, Eriobotrya japonica Lindley, Amomum tsao-ko Crevost et Lemaire, Cornus officinalis Siebold et Zuccarini, Forsythia koreana Nakai, Ulmus darvidian for. Suberose, Polygonum aviculare Linne, and Geraniumthunbergia. Siebold et Zuccarini [229] and Bahmani et al. [230] reported that a combination of ephedrine and caffeine, capsicin from red pepper and chili, yohimbine, guar gum extracted from the plant Cyamposistetragonolobus, glucomannan extracted from the root of Amorphophalluskonjac, Garcinia cambogia, the active ingredient from Pausinystalia- johimbe, and Hoodia gordonni have functional roles in reducing weight, improving energy, and inhibiting fat absorption, with no negative impacts in the treatment groups. The most principal medicinal plants and herbs in traditional Chinese medicine in the treat- ment of obesity are celastrol (Tripterygium wilfordii), Berberine (Coptis chinensis), Capsaicin (Chili pepper), Resveratrol (Polygonum cuspidatum), Chrysophanic acid/Rhein (Rhubarb), (Trigonella foenumgraecum L.), Curcumin (Turmeric), Radix astragali, Tea cate- chins GTpolyphenols (Green tea), Xiexin decoction, white tiger plus ginseng decoction, and Chaihu Shugan powder through increased leptin sensitivity, blocking fat production and accumulation, improving lipid decomposition, regulating the level of adiponectin, etc. [231,232]. Polyphenol, quercetin, caffeic acid, hydroxyflavin, and hesperetin are ac- tive constituents of mulberry leaf with possible anti-obesity impacts [233]. Capsicoside G is the main component of pepper which can block adipogenesis through activation of adenosine monophosphate-activated protein [234]. The principal active component of cocoa with anti-obesity activity is polyphenols which decrease lipids in the liver; genes in lipid catabolism, primarily in fatty acid oxidation, was up-regulated, whereas genes in lipid synthesis pathways were down-regulated, regulating obesity-induced steatosis markers [235]. Coumaric acid and ferulic acid are the main anti-obesity components of barley which may inhibit adipocyte differentiation, dysregulate lipid profiles, and prevent body weight gain [236]. Black soybean contains anthocyanin, which can markedly alleviate fat accumulation, regulate the expression of lipogenesis genes (acetyl-CoA carboxylase), and improve the levels of lipolysis proteins (hormone-sensitive lipase, lipoprotein lipase, and adenosine monophosphate-activated protein kinase) in mesenteric fat [237]. The ac- tive anti-obesity of red chili pepper, capsinoids, can suppress diet-induced obesity via uncoupling protein 1-dependent mechanism [238]. The most notable active components of garlic are S-allyl-l-cysteine sulphoxide, S-allyl cysteine which can alleviate relative masses of liver and fat tissues, hepatic oxidative stress levels, serum triacylglyceride levels, and improve fecal lipid contents in high fat diet rats, up-regulated adenosine monophosphate- activated protein kinase, adipose triacyglyceride lipase, Sirtuin 1, hormone-sensitive lipase, palmitoyltransderase 1, Acyl-CoA oxidase, whereas it down-regulated cluster of differentia- tion 36 [239]. Crocin of saffron can significantly alleviate total cholesterol and plasma levels of triacylglycerol [240]. Tiliroside of raspberry and strawberry may inhibit obesity-induced hepatic inflammation and muscular triglyceride accumulation [241]. Polyphenols are the Appl. Sci. 2021, 11, 7889 13 of 23

active anti-obesity constituent of coffee which can regulate postprandial hyperglycaemia and hyperlipidemia, suppress lipogenesis by down-regulating sterol regulatory element- binding proteins acetyl-CoA carboxylase-1 and -2, stearoyl-CoA desaturase-1 and pyruvate dehydrogenase kinase-4 in the liver [242]. Anthocyanidins of bilberry can block adipocyte differentiation through impacting the gene expressions of the insulin pathway, reduced PPAR, sterol regulatory element-binding protein 1c and tyrosine residues of insulin receptor substrate 1 phosphorylation [243].

6. Conclusions Many chronic diseases, asthma, etc. are associated with obesity and overweight, and the dramatic rise in obesity prevalence worldwide has become a real health concern. As obesity is a risk factor for many diseases, obesity itself may worsen the outcomes of COVID-19, which may require intensive care. Obesity/overweight is linked with increase COVID-19 mortality, and the monotonic relationship between COVID-19 infection and body mass index and risks of hospitalization have been reported. The main reasons which may contribute to obesity are reduced physical activity, excess intake of calorie loaded food, depression, pharmaceutical concomitant, food obsession, personality traits, geni- tal/hereditary predisposition, economic growth, and lifestyle modifications. Medicinal plants, particularly edible plants have long been used as traditional knowledge to treat and prevent obesity, especially in Asian countries, because various bioactive compounds from both herbs and fruits have been found useful for anti-obesity drug discovery and develop- ment processes. Obesity is an important problem for normal growth in children, with both primary and secondary health risks such as high blood pressure, insulin resistance, hyper- tension, cardiovascular diseases, and different cancers. The different mechanisms which medicinal plants may affect weight loss consist of increasing levels of leptin, hypolipidemic and hypoglycemic effects, reducing fat absorption, influencing fat metabolism, enhancing metabolism, decreasing appetite, and preventing carbohydrate intake. The most important medicinal plants which are common in traditional medicinal sciences of different countries due to their anti-obesity activities are Acosmium dasycarpum (Vog.) Yakovlev, Allium cepa L., Aloe barbadensis Miller, Amorphophallus konjac K. Koch., Artemisiasphaerocephala Krasch, Betula utilis, Bupleuri Radix, Butea monosperma, Caralluma fimbriata, Corchorus olitorius L., Cuminum cyminum L., Carum carvi L., Cyclopia spp., Cynara scolymus L., Cynometra cauliflora Linn., Cynomorium songaricum Rupr., Echium angustifolium Mill., Echium angustifolium Mill., Garcinia cambogia, Gnidia glauca (Fres.) Glig, Ganodermalucidum sensu strict, Gnidia glauca (Fres.) Glig., Hibiscus sabdariffa L., Ilex paraguariensis, Justicia carnea Lindl., Juniperus commu- nis L., Ligustrum robustum Blume, Lobelia chinensis lour, Macrotyloma uniflorum (Lam.) Verdc., Mangifera indica Linn., Melissa officinalis L., Memecylon umbellatum Burm. f., Moringa oleifera Lam., Moringa peregrine (Forssk.) Fiori., Morus alba L., Nigella sativa L., Oroxylum indicum Kurz, Passiflora edulis Sims, Pilosocereusgounellei (F.A.C. Weber) Byles and G.D.Rowley, Piper nigrum L., Populus balsamifera L., Psidium guajava L., Raphanus sativus L., Salacia chi- nensis L., Salvia hispanica L., Salviaofficinalis L., Smilax china L., Smilax glabra Roxb., Solenos- temma argel Hayne, TabebuiaavellanedaeLorentz ex Griseb, Tinospora cordifolia (Thunb.) Miers., Urtica dioica L., Vaccinium arctostaphylos L., and Withania somnifera (L.) Dunal.

Author Contributions: W.S.: writing—original draft preparation; M.H.S.: writing—original draft preparation; Q.C.: writing—review and editing. All authors have read and agreed to the published version of the manuscript. Funding: This research was funded by the Natural Science Foundation of Beijing, China (Grant No.M21026). This research was also supported by the National Key R&D Program of China (Research grant 2019YFA0904700). Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: Not applicable. Appl. Sci. 2021, 11, 7889 14 of 23

Conflicts of Interest: The authors declare no conflict of interest.

Abbreviations T2D: type 2 diabetes; BMI: body mass index; ICU: intensive care unit; IMV: invasive mechanical ventilation; TNFα: tumor necrosis factor alpha; IL: interleukin; ARDS: acute respiratory distress syndrome; TC: total cholesterol; HFD: high-fatdiet; EWAT: epididymal white adipose tissue; PPARγ: peroxisome proliferator-activated receptor γ; NBP: 3-N-butylphthalide; Sirt1: Sirtuin 1; GSF: grape seed flour; BupE: Bupleuri Radix extract; WFA: Withaferin A; MAPK: mitogen-activated protein kinase; AMPK: AMP-activated protein kinase; HQS: Huang-Qi San.

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