Table 4.

Scientific evidence of the most representative species of the genus Ficus L. on diabetes and obesity

Type of Study	Extract or phytochemical/Plant part	Objective and biological effect	Ref
F. carica
In vivo	Aqueous/leaves	Since excessive lipid storage affects the net yield of poultry meat, it was questioned whether the dietary supplement of the extract could decrease TG and T-Cho content in livers of 8-week-old roosters. It was concluded that the extract drastically decreased the level of TG and the secretion of Cho depending on the concentration of the extract	[110]
In vivo	Flavonoids/fruits (FFc) and leaves (LFc)	This study was developed to identify the flavonoid content in the fruit (FFc) and leaves (LFc) and to investigate its Action on blood sugar level, daily food intake, body weight gain, feed efficiency ratio, serum lipid profile, renal function and liver function in diabetic rats. Phytochemical analysis of FFc and LFc revealed the presence of progalic acid, ferulic acid, coumaric acid, galangin, cinnamic acid, and pinostorbin quercetin. The elevation of sugar in the rats injected with Allox improved when. FFc and LFc were included in their diet. In addition, both hypercholesterolemia and hyperlipidemia, as well as hepatic and renal functions improved remarkably. Presumably, the antioxidant power, the fiber content and the presence of flavonoids in FFc and LFc were the bases for such beneficial reactions	[111]
In vivo	MeOH/Leaves (MELFc)	The objective of the research was to determine the antidiabetic effect of the extract (MELFc) in allox-induced diabetic rats. MELFc administration (200 mg/kg p.o. dose) showed a reduction in blood glucose and TG levels; as well as a significant improvement in body weights	[112]
In vivo	Aqueous/leaves (AELFc)	Joerin et al. investigated the preventive potential of the extract (AELFc) on hyperlipidemia in obese male Sprague-Dawley rats induced by a high-fat diet (HFD). The benefit of AELFc was more significant than pioglitazone (positive control), since it significantly improved the lipid profile (T-Cho, TG, and LDL) and decreased interleukin-6 (IL-6) levels and adipogenic risk factors; probably attributed to an improvement in HDL levels	[113]
In vivo	Leaves	The study evaluated the antioxidant, antilipidemic, and antidiabetic effects of ficusin isolated from F. carica and its action on GLUT4 translocation and PPARγ expression in HFD-STZ-induced type 2 diabetic rats. Ficusin (20 and 40 mg/kg doses) decreased serum antioxidant enzyme levels (SOD, CAT, and GPx), lipids, plasma insulin, and fasting blood glucose concentrations to nearly normal values. It also improved the PPARγ expression and GLUT4 translocation and activation in adipose tissue; suggesting promising interactions of GLUT4 and PPARγ at their active sites	[106]
In vitro	EtOH/fruits, leaves, and stem bark	The role of some extracts from the aerial parts of F. carica in the antioxidant, antidiabetic and antiobesogenic effects was studied. In addition, their content of polyphenols and flavonoids was estimated. The EtOH extract of the fruits was the most significant by inhibiting α-amylase and α-glucosidase (antidiabetic capacity), reducing antilipase activity (antiobesogenic potential) and showing a high antioxidant effect (attributed to a high amount of polyphenols and flavonoids)	[114]
In vivo	EtOAc/leaves	The action of an EtOAc extract on glucose, lipid and carbohydrate metabolism enzyme levels in HFD-STZ-induced type 2 diabetic Wistar rats was determined. After 28 days of administering the extract (250 and 500 mg/kg), they demonstrated a positive action on oral glucose tolerance (OGTT), intraperitoneal insulin tolerance test (ITT), T-Cho, TG, and body weight. Furthermore, the activity of G6Pase, fructose-1,6-bisphosphatase and hexokinase in liver tissue was enhanced. An immunohistochemical study confirmed the protective effect of pancreatic β cells	[115]
In vitro	Aqueous-EtOH/two cultivars (Whole plant)	Using a Chromatography-Diode Array Detection-Electrospray Ionization-Quadrupole Time-of-Flight-Mass Spectrometry (HPLC-DAD-QTOF-MS) analysis, the phenolic components of an aqueous-EtOH extract were studied. Finding mainly dihydroxybenzoic acid, dipentoside, rutin, psoralen and methoxypsoralen. With this result, we proceeded to determine the hypoglycemic, lipid-lowering and antioxidant activities of both cultivars in diabetic rats induced by allox. The extract improved the lipid profile and the blood glucose level. Likewise, the activity of antioxidant enzymes present in liver and heart tissue, increased	[116]
In vivo
In vitro	Aqueous, Hx, EtOAc and EtOH/fruit, leaves and stem bark	Different types of extracts were obtained from which their total content of polyphenols and flavonoids was estimated. Subsequently, its antioxidant, antidiabetic and antiobesogenic effects were demonstrated. The use of GC/MS showed that the EtOH extract of the fruits contained the highest amount of polyphenols and flavonoids (highlighting butyl butyrate, 5-hydroxymethyl furfural, 1-butoxy-1-isobutoxy butane, malic acid, tetradecanoic acid, phytol acetate, trans phytol, n-hexadecanoic acid, stearic acid, sitosterol, and 2,4,5-trimethyl-2,4-dihydro-3H-pyrazol-3-one). This set of phytochemicals is possibly responsible for inhibiting α-amylase, α-glucosidase, and antilipase	[117]
In vivo	MeOH/leaves (MELFc) and branches (MEBFc)	Using methanolic extracts, their protective effects were investigated in hyperlipidemic Swiss albino mice induced by Triton WR-1339. Also, their contents of phenols, flavonoids and anthocyanins, and their antioxidant activities were determined by means of DPPH*, (2,2-Diphenyl-1-Picrylhydrazil), ABTS*+ (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) and iron reducing capacity of plasma (FRAP). After 24 hours of administration to MELFc and MEBFc in doses higher than 5,000 mg/kg, no signs of toxicity were evident. Conversely, blood tests indicated a decrease in TG, T-Cho, and LDL levels, while HDL increased. Likewise, the DPPH*, ABTS*+ and FRAP trials demonstrated its high antioxidant potential. The suggestion is that flavonoids and anthocyanins may have a synergistic effect on hyperlipidemia	[103]
Clinical study	Abscisic acid (ABA)/fruits	This investigation examined the protective effect of two fig fruit extracts (FFEs), each administered in two different doses of ABA, on the glycemic index (GI) and insulinemic index (II) of a standard glucose drink ingested by healthy adults. Test beverages contained 200 mg FFE-50× and 1,200 mg FFE-10× and were ingested by subjects with postprandial glucose and insulin assessed at regular intervals for 2 h to determine GI and II responses. After supplementing both doses, the GI and II values were significantly reduced; suggesting that FFEs may be a promising nutritional intervention for the management of insulin homeostasis	[118]
In vivo	MeOH/Whole plant	The protective effect of F. carica (CEFc) was evaluated in type 2 diabetic Wistar rats induced by HFD-STZ. CEFc (250 mg/kg/day) controlled DM2 by reducing body weight, serum glucose, T-Cho, TG, LDL, and very-low-density lipoproteins (VLDL); It also increased the beneficial effect of HDL and SOD	[119]
In vivo	MeOH/seeds	The purpose of the study was to compare and investigate whether the extracts of F. carica (MESFc) and Lepidium sativum (MESLs) showed any protective effect on blood sugar levels in normal and diabetic rats induced with STZ. For five weeks, MESFc and MESLs (100 and 200 mg/kg) were administered v.o., and at the end of this period glucose levels, lipid profile, and liver enzymes remarkably restored. A significant increase in HbA1c levels was also observed. However, the most significant beneficial effect corresponded to MEFcS	[120]
In vitro	Flavonoids/fruit peel	Extracts rich in flavonoids were tested against five enzymes (α-glucosidase, tyrosinase, urease, acetylcholinesterase, and butyrylcholinesterase) and their antioxidant activities were evaluated. The extracts were mainly effective in inhibiting tyrosinase and α-glucosidase. However, all the extracts showed a relevant antioxidant potential. On the other hand, the phytochemical analysis revealed large amounts of flavonoids (mainly flavonols, 81%). Since F. carica has shown hypoglycemic action, its flavonoids could be considered multifunctional bioactive ingredients to be used in pharmaceutical formulations	[121]
In vivo	EtOH/leaves	Despite fig leaves have been shown to lower blood glucose levels, their collection and use are not entirely practical or consistent. For this reason, this research determined the antidiabetic efficiency of an extract using dosages formulated in tablets. Three formulations were prepared with doses of 40, 60 and 80 mg of the extract and administered for 14 days to diabetic rats induced with allox. The results proved that all three types of tablets lowered blood glucose levels	[122]
F. racemosa
In vivo	EtOH/stem bark (EEBFr)	The aim of the study was to investigate the antihyperglycemic and hypolipidemic activity of the extract (EEBFr) in alloxan (Allox)-induced diabetic rats. Oral administration (100-500 mg/kg) of EEBFr reduced glucose, T-Cho, TG, and HDL levels in Allox-treated rats in a dose-dependent manner	[123]
In vivo	Ace/stem bark	After separating a tannin fraction (TF) from the extract, two doses (100 and 200 mg/kg) were orally administered (v.o.) to hypercholesterolemic and diabetic rats to evaluate their effects on lipid and antioxidant profiles. Administration of TF supplementation reversed the STZ-induced increase in blood glucose and decreased the elevated levels of T-Cho, TG, and LDL caused by the high-fat diet. Additionally, the antioxidant status was improved by restoring the activity of SOD, CAT and decreasing GSH-Px	[124]
Clinical study	Aqueous/stem bark	In order to know the hypoglycemic effect of F. racemosa in diabetic patients who were taking sulfonylureas, they were suggested to ingest 5 ml (approximately 100 mg) of an extract of its bark twice a week for 15 days. At the end of the period, blood samples where there was a notable decrease in the sugar level an hour and a half after breakfast were analyzed. Normal values of bilirubin, alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein and urea were presented	[125]
In vivo	Flavonoids/stem bark	Using infrared spectroscopy and nuclear magnetic resonance, four flavonoids were isolated and administered once a day for one week to diabetic rats. The results indicated that its flavonoids (100 mg/kg dose) reduced the blood glucose level and the body weight of the animals increased by the STZ. There was a decrease in lipid profile parameters. Besides, oxidative stress biomarkers and liver enzymes were normalized. In addition, coupling studies suggest that the antidiabetic potential of flavonoids is related to PPARγ and GLUT1 receptors	[126]
F. religiosa
In vivo	Aqueous/stem bark (AEBFr)	Evidence indicate that OXs is related to the pathogenesis of DM2. Therefore, the potential of the extract (AEBFr) to lower fasting blood glucose in diabetic Wistar rats induced by STZ was evaluated. Orally administered doses of AEBFr (100 and 200 mg/kg) modulated and restored antioxidant enzymes [CAT, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD)] to normal values. In addition, the highest dose significantly lowered blood glucose	[127]
In vivo	Aqueous/stem bark (AEBFr)	Pandit et al. investigated the effect of oral administration (25, 50 and 100 mg/kg) of the extract in normal, glucose loaded, hyperglycemic and diabetic rats induced by STZ. The three doses caused a reduction in blood glucose in all the experimental models. In addition, higher doses increased serum insulin, body weight, and liver glycogen content. Such phenomena are comparable to glibenclamide. AEBFr also presented an antilipoperoxidative effect by reducing the levels of TG and T-Cho	[128]