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Potencial antidiab�tico de extractos de Higo (Ficus Carica) para el tratamiento de la diabetes mellitus tipo II

 

Antidiabetic potential of fig (Ficus carica) extracts for the treatment of type II diabetes mellitus

 

Potencial antidiab�tico de extratos de figo (Ficus carica) para o tratamento da diabetes mellitus tipo II

 

 

 

 

 

 

 

 

 

 

 

Correspondencia: dnaranjo@clonallyxcorporation.org

 

Ciencias de la Salud

Art�culo de Investigaci�n

 

* Recibido: 26 de julio de 2025 *Aceptado: 22 de agosto de 2025 * Publicado: �18 de septiembre de 2025

 

       I.          Departamento de Biolog�a molecular. Centro de Biociencias Clonallyx Corporation. Quito, Ecuador.

     II.          Departamento de Biolog�a molecular. Centro de Biociencias Clonallyx Corporation. Quito, Ecuador.

   III.          Departamento de Biolog�a molecular. Centro de Biociencias Clonallyx Corporation. Quito, Ecuador.

   IV.          Departamento de Biolog�a molecular. Centro de Biociencias Clonallyx Corporation. Quito, Ecuador.

 

Resumen

La medicina tradicional ha sido el apoyo de la humanidad durante cientos de a�os, brindando un sinf�n de soluciones para diversas enfermedades al igual que una gran cantidad de beneficios nutricionales para la salud. Esta se enfoca en el uso de plantas medicinales, donde se puede encontrar un sin n�mero de componentes qu�micos con propiedades medicinales �nicas. En ese contexto, el higo, cuyo nombre cient�fico es Ficus Carica, es una planta perteneciente a la familia Moraceae que ha sido utilizada en la medicina tradicional debido a su potencial farmac�utico. Este �rbol de sabia lechosa, ramas dispersas, frutos en forma de pera y hojas similares a las de la papaya posee diversos componentes como fitoesteroles, flavonoides, amino�cidos, antocianinas, �cidos org�nicos, entre otros. Adem�s, posee efectos antioxidantes anticancer�genos, antiinflamatorios e hipolipid�micos. Estos componentes son usados para el tratamiento de diversas afecciones end�crinas, respiratorias, gastrointestinales y reproductivas. De igual manera, brinda un excelente potencial antidiab�tico para disminuir la cantidad de glucosa en la sangre. Por esta raz�n, el objetivo de esta revisi�n es el an�lisis del potencial antidiab�tico de Ficus Carica contra la diabetes tipo II , determinar cu�les componentes generan dicho efecto, y describir nuevos tratamientos antidiab�ticos naturales con una mayor eficiencia y menos efectos adversos.

Palabras Clave: Higo (Ficus Carica); planta medicinal; actividad antidiab�tica; medicina tradicional; diabetes tipo II.

 

Abstract

Traditional medicine has supported humanity for hundreds of years, providing countless solutions for various diseases as well as a wealth of nutritional health benefits. It focuses on the use of medicinal plants, where a number of chemical components with unique medicinal properties can be found. In this context, the fig, whose scientific name is Ficus carica, is a plant belonging to the Moraceae family that has been used in traditional medicine due to its pharmaceutical potential. This tree with milky sap, scattered branches, pear-shaped fruits, and papaya-like leaves possesses diverse components such as phytosterols, flavonoids, amino acids, anthocyanins, and organic acids, among others. It also has antioxidant, anticancer, anti-inflammatory, and lipid-lowering effects. These components are used to treat various endocrine, respiratory, gastrointestinal, and reproductive conditions. It also offers excellent antidiabetic potential by lowering blood glucose. For this reason, the objective of this review is to analyze the antidiabetic potential of Ficus Carica against type II diabetes, determine which components generate this effect, and describe new natural antidiabetic treatments with greater efficiency and fewer adverse effects.

Keywords: Fig (Ficus carica); medicinal plant; antidiabetic activity; traditional medicine; type II diabetes.

 

Resumo

A medicina tradicional apoia a humanidade h� centenas de anos, fornecendo in�meras solu��es para v�rias doen�as, bem como uma riqueza de benef�cios nutricionais para a sa�de. Foca-se na utiliza��o de plantas medicinais, onde se podem encontrar uma s�rie de componentes qu�micos com propriedades medicinais �nicas. Neste contexto, o figo, cujo nome cient�fico � Ficus carica, � uma planta pertencente � fam�lia Moraceae que tem sido utilizada na medicina tradicional devido ao seu potencial farmac�utico. Esta �rvore com seiva leitosa, ramos dispersos, frutos em forma de pera e folhas semelhantes � papaia possui diversos componentes, como fitoester�is, flavonoides, amino�cidos, antocianinas e �cidos org�nicos, entre outros. Tem ainda efeitos antioxidantes, anticancer�genos, anti-inflamat�rios e hipolipemiantes. Estes componentes s�o utilizados para tratar diversas condi��es end�crinas, respirat�rias, gastrointestinais e reprodutivas. Oferece ainda um excelente potencial antidiab�tico, reduzindo a glicemia. Por este motivo, o objetivo desta revis�o � analisar o potencial antidiab�tico do Ficus Carica contra a diabetes tipo II, determinar quais os componentes que geram este efeito e descrever novos tratamentos antidiab�ticos naturais com maior efic�cia e menos efeitos adversos.

Palavras-chave: Figueira (Ficus carica); planta medicinal; atividade antidiab�tica; medicina tradicional; diabetes tipo II.

 

Introducci�n

The prevention and treatment of metabolic diseases which affect the cardiovascular system are fundamental to ensure community�s life quality. Type II diabetes (T-IID) is a chronic disease with high level prevalence and mortality worldwide which is increasing in epidemiological scale nowadays (Cordero et al., 2017). According to the International Diabetes Federation (IDF), approximately 700 million adults will be diagnosed with this disease by 2040 (Parissis et al., 2023). This affection produces the degeneration of β-cells in pancreas, avoiding the enough insulin release to metabolize glucose in the body, producing metabolic problems (Franco Quinde et al., 2018) (Leahy, 2005). As a result, type II diabetes is the main cause of cardiovascular, cerebrovascular, renal diseases and non-traumatic amputations (Cordero et al., 2017) (DeFronzo et al., 2015). To fight against this disease, several treatments are used, taking drugs like metformine and insulin injections (Patel et al., 2023) (Bitew et al., 2021). Metformine reduces the basal hyperinsulinemia by diminishing the hepatic glucose production. It is also employed by prediabetic patients to avoid the development of the disease (Patel et https://orcid.org/0009-0000-9785-6494al., 2023). However, the prolonged use of this drug can produce renal damage and failure (Yang et al., 2014). In the case of insulin, it is an antidiabetic molecule involved in glucose absorption by tissues. This administration of this treatment is only required when patients do not have the capacity to produce enough insulin by themselves (Rodr�guez, 2022). In Ecuador, metformine is one of the most used treatments by diabetic population. However, usually, there is a shortage of it in public health institutions, and diabetic Ecuadorian patients do not have enough economic resources to acquire it (Zavala Calahorrano & Fern�ndez, 2018). On the other hand, insulin cannot be used in all diabetic patients due to their pancreatic function is good enough. For these reasons, research into novel and more effective treatments for diabetes control is fundamental to maintain population health and disease control. Based on the previous background, fig (Ficus Caroca) can be used as phytotherapy against type II diabetes due to its antihyperglycemic activity (Reyes-Castro et al., 2021). Some fig compounds like quercetin and dichloromethane can help to balance glucose levels in blood, protect pancreatic β-cells and ensure cardiovascular system capacity (Lin & Zhang, 2023). Therefore, this bibliographic review aims to determine which are fig extract benefits for human health, focusing on type II diabetes treatment to improve drug availability against this disease.��

1. Fig (Ficus Carica) features and medicinal properties.

Ficus Carica is one of the most recognized plants around the world. Commonly known as �fig�, it is one of the favorite delicacies for their sweet flavor and soft texture. It belongs to Moraceae family, Ficus genus and Carica specie, reason why it displays characteristic� papaya-like leaves (Badgujar et al., 2014) (Hj. Idrus et al., 2018) (Jabeen et al., 2023). This plant is native to Sub-Himalayan, and it can be grown in temperate climates (Badgujar et al., 2014) (Arsyad et al., 2022). Structurally, fig tree can reach 15�20 ft (9-12 m) in height and 10m wide. Morphologically, fig roots are shallow and fibrous whereas the trunk is made of soft wood which divides into massive spreading branches. Fig leaves are green, and they have a particular finger-chape of 3 to 5 segments (Figure 1) (Faramayuda et al., 2022). Fig fruit exhibits a pear shape, and they are placed axillary on leafy branchlets. They can present several colors based on their maturation time between green and purple (Mohamad Hesam Shahrajabian et al., 2021). Finally, fig latex is a sticky solution composed of single cells. This milky exudate produces skin� irritation due to several proteolytic enzymes (Faramayuda et al., 2022).

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Figure 1: Fig leaves and fruit

 

Other distinctive structure is fig tree latex which is a milky white solution that contains a protein hydrolytic enzyme called ficin, which has pharmacological properties (Badgujar et al., 2014) (Barolo et al., 2014). Usually, fig fruit is used in dessert preparations and pigment industry. However, this plant can be used in wide research and industrial fields, especially in the pharmaceutical one, where have been used by traditional medicine over the years thanks to its several medicinal benefits (Mohamad Hesam Shahrajabian et al., 2021) (Dogara et al., 2024). It has been used to treat endocrine, respiratory, gastrointestinal and reproductive affections (Nuri & Uddin, 2020) (Arsyad et al., 2022). Moreover, it contains several amounts of vitamins, chemical compounds and nutrients to keep body�s health high quality (Hj. Idrus et al., 2018). As well, figs are excellent sources of� minerals, carbohydrates, lipids, enzymes� and phenolics (Hajam & H, 2022). These molecules can be used pharmaceutically as antioxidant, anticancer, cytotoxic, anti-inflammatory and hypolipidemic agents (Hj. Idrus et al., 2018) (Kucukerdonmez et al., 2021) (Abdel-Rahman et al., 2021) (Mennane et al., 2021). More examples of medical uses of fig extracts are described in Table 1. Therefore, these properties can be used to improve people�s health in the treatment of type II diabetes.

 

 

Phytochemically, Ficus Carica contains several molecules like phytosterols, flavonoids, triterpenoid, amino acids, anthocyanins, organic acid, fatty acids, carbohydrates, phenolic components, aliphatic alcohols and secondary metabolites that are placed principally in its latex, leaves, root and fruit (Figure 2) (Badgujar et al., 2014) (Murthy & Bapat, 2020) (Rasool et al., 2023) (Hajam & H, 2022) (Fazel et al., 2024). As well, fig possesses phenolic acids like quercetin-3-O glucoside, 3-O- and 5-O-caffeoylquinic acid, ferulic acid, bergapten, psoralen and other organic acids (Hajam & H, 2022). More examples of secondary metabolites found in fig leaves extracts are coumarin, triterpenoids like lupeol acetate, oleanolic acid, bauerenol; aldehydes such as 2-methylbutanal; ketones: 6 methyl-5-hepten-2-one, monoterpenes and esters: ethyl salicylate, methyl salicylate, and methyl hexanoate� (Faramayuda et al., 2022).

 

 

 

 

 

 

 

Figure 2: Phytochemistry of Ficus Carica-main compounds

 

2. Fig (Ficus Carica) application for diabetes type II treatment.

Traditional medicine has been a fundamental support to treat diseases in several cultures. For that reason, the use of plants as natural pharmacological agents is one of the most effective mechanisms to create new treatments without cytotoxicity and side effects (Priyoherianto & Saputra, 2018). One plant that has been used in traditional medicine over time is fig (Ficus Carica) thanks to its antioxidant, hepatoprotective, anti-inflammatory and hypoglycemic properties (Gupta et al., 2022). So, it can be considered as a candidate to be applied in phytotherapy to treat type II diabetic patients (P�rez et al., 2000). Nowadays, synthetic drugs used to treat this disease contain biguanides, sulfonylureas, thiazolidinediones, SGLT2 inhibitors and GLP-1 agonists (Gupta et al., 2022). These treatments can stabilize blood sugar levels, but unfortunately, they produce several side effects like insulin resistance, gastrointestinal adverse reactions, risk of edema, heart failure and weight gain when they are prolonged used (Gupta et al., 2022). For this reason, the creation of new and novel natural drugs based on plant-derived substances with better pharmacological effects and less side effects is crucial.

 

3.1.    Clinical trials features: population, goals and results.

Therefore, fig can be an excellent choice to create antidiabetic treatments (P�rez et al., 2000). To determine fig properties, the procurement of extracts from its leaves, fruit and seeds by decoction is required followed by clinical trials where these chemical solutions will be tested into diabetic rats. According to several researchers, aqueous fig leaves extracts (AFLE) have the capacity to decrease glucose levels. Also, they can contain active components that protect pancreatic cells (Gupta et al., 2022) (Stephen Irudayaraj et al., 2017). Other hypothesis supposes that these extracts have the capacity of minimizing insulin dosage. In the case of methanolic fig leaves extract (MeOH FL), they have the ability to attenuated pancreatic β-cell damage and inhibit α- glucosidase and α-amylase, which are enzymes responsible of blood sugar control and carbohydrate catabolism (Gupta et al., 2022). Other details related to clinical trials are shown in Table 2.

During experiments, several mice and rat models were employed to simulate the disease, expressing high glucose levels in blood, like a diabetic person. The induction of diabetes symptomatology was performed using drugs like alloxan monohydrate, Glibenclamide and streptozotocin (Aisyah et al., 2023; Gupta et al., 2022; Kurniawan & Yusuf, 2021; Lin & Zhang, 2023; P�rez et al., 2000; Priyoherianto & Saputra, 2018; Saleem et al., 2023).� In terms of applied treatments, three main types of dilutants were employed: water for aqueous solutions, ethanol and methanol (Aisyah et al., 2023; Choi et al., 2024; Kurniawan & Yusuf, 2021; Mahanem et al., 2024; P�rez et al., 2000; Priyoherianto & Saputra, 2018; Saleem et al., 2023). Other studies employed Dichloromethane and Ethyl acetate (Gupta et al., 2022; Lin & Zhang, 2023; Stephen Irudayaraj et al., 2017).� Doses applied during treatment vary in concentration, duration, number of doses and application mechanism.��� Finally, results described in all trials report the reduction of glucose levels in blood as well as protective effects in pancreas, cholesterol and triglycerides reduction, among others.

 

 

 

 

Table 2: Studies to determine antidiabetic properties of Fig extracts

 

3.2.����� Clinical trials: experimental assay and statistic results

Results of some studies related to the antidiabetic effect of fig extracts are shown in Table 3. To analyze the hypoglycemic effects of fig extracts, several glucose parameters related to sugar levels were measured in blood samples using biochemical analysis. The tests include the analysis of fasting blood glucose (FBG) and serum glucose principally (Aisyah et al., 2023; Choi et al., 2024; Gupta et al., 2022; Kurniawan & Yusuf, 2021; Lin & Zhang, 2023; P�rez et al., 2000; Priyoherianto & Saputra, 2018; Saleem et al., 2023; Stephen Irudayaraj et al., 2017). Other studies complemented their analysis by studying other parameters like insulin measurements, glucose tolerance test, blood lipids, histological analysis, among others (Choi et al., 2024; Gupta et al., 2022; Lin & Zhang, 2023; Saleem et al., 2023).

During clinical trials, healthy rats were considered as a negative control group. By contrast, rats who were only exposed to drugs to induced diabetes were used as positive control to assess glucose values of diabetic patients. Kurniawan & Yusuf, 2021 describe glucose levels of 554 � 47 mg/dl in their positive control. Other example was described by Saleen et al., 2023 where his positive group displayed 345.74�12.77 mg/dL glucose level. After the first glucose level evaluation, diabetic rats were exposed to commercial drugs to determine chemical treatment effectiveness. Commercial drugs employed as antidiabetic treatments were Glibenclamide and Metformine. Some results of glucose levels reduction are described by Priyoherianto & Saputra, 2018 with a decrease of 44.3% using Glibenclamide; Mahanem et al., 2024 report a greatly reduction from 24.42�3.27 mmol/L to 13.22�0.81 mmol/L after 21 days of metformine treatment; Aisyah et al., 2023 indicate a decrease of 45.8% using Glibenclamide; Kurniawan & Yusuf, 2021 described a decrease of 30-40% of glucose levels approximately using metformine.

By contrast, fig extract used during trials were made of fig leaves and fruits. The doses applied during clinical assessments were different in each study and they depended on the authors. Also, all of fig treatments display similar antidiabetic effects compared to commercial diabetes treatments. So, they decreased glucose levels to normal or almost healthy rates. Evidence of the antidiabetic effect of fig extracts is described by Gupta et al., 2022 with a reduction of� glucose in blood of 35.75% and 44.17% when he applied doses of 500 and 1000 mg/kg, respectively; Priyoherianto & Saputra, 2018 report blood reduction applying 100 mg/kg dose (17.3%), 300 mg/kg dose (29.3%), 600 mg/kg dose (35.2%); Aisyah et al., 2023 describe a reduction of 29.1%, 46.6% and 83.9% when rats are treated with 5%, 10% and 15% of fig extracts. Results of other clinical trials can be observed in Table 3. This comparison demonstrates that fig extracts have hypoglycemic potential, like chemical treatments. In addition, they present few or null side effects. The mechanism of action of fig-derived compounds is usually unknown, but researchers propose an undefined insulin-like peripheral effect (P�rez et al., 2000).� Also, other beneficial features of fig extracts have been described during clinical trials are erythrocyte catalase level normalization and plasma vitamin E increase (P�rez et al., 2000). The statistical analysis employed ANOVA test due to the nature of the experiments with different p-values to express significant differences between positive control groups and those treated with fig extracts. Finally, all researches conclude that Ficus Carica extracts have a good antidiabetic potential with similar antidiabetic effects as commercial treatments.� Also, they emphasize the importance of developing a mechanism to administrate correct dosages of fig leaves-derived compounds.

 

 

 

 

 

Table 3: Statistical results of clinical trials.

 

1. Antidiabetic potential of flavonoids and additional fig benefits

Based on the previous sections, Ficus Carica has several substances with excellent medical properties, which can be employed as pharmaceutical treatments for diverse diseases, including type II diabetes. One of them are flavonoids, that are phenolic compounds synthesized by plants which usually give the orange-red colors to them (Dias et al., 2021). In Ficus Carica, the major flavonoids amount are in the fruit, and it is� directly proportional to the maturation time (Rahmasita et al., 2021). Also, flavonoids can be found in other fig tree structures like leaves (Zhao et al., 2021). As therapeutic treatments, flavonoids have the capacity to modulate several enzymatic activities that can help human health. The most important medical potential of flavonoids is their excellent antioxidant activity (Juc� et al., 2020) (Ullah et al., 2020) (P�rez et al., 2003). Some other beneficial properties are their anti-inflammatory, antimicrobial, antiviral, antiparasitic and antifungal activities, and their cardioprotective efgfects (Juc� et al., 2020).

In the case of their antidiabetic effect, flavonoids present inhibitory effects of digestive enzymes, reduction of the glucose absorption and starch hydrolysis avoidance (Bitew et al., 2021). As a result, glucose levels decrease in blood. For this reason, flavonoids constitute one excellent candidate to be used as treatment against type II diabetes (Cahyana & Adiyanti, 2021) .� In the case of the flavonoids inhibitory effect of digestive enzymes, they work on α-amylase and α-glucosidase, responsible of degrade carbohydrates in the mouth and intestine, respectively (Cahyana & Adiyanti, 2021). This inhibition happens by the bond between hydroxyl groups on flavonoids and enzyme catalytic residues (Hussain et al., 2020) (Shamsudin et al., 2022). Thus, the enzymatic activity decreases, reducing the amount of glucose metabolism, and hence, diminishing the amount of glucose that can be absorbed by the body. Consequently, the glucose level in blood will decrease. In the case of starch hydrolysis avoidance, flavonoids can form molecule complexes called �resistant starch� when they match natural starch (Cahyana & Adiyanti, 2021). As a result, this new starch complex is more resistant to degradation by digestive enzymes, reducing the amount of glucose available to be absorbed by the body. Finally, flavonoids can reduce glucose absorption by the inhibition of glucose transporters SGLT and GLUT at the small intestine (Cahyana & Adiyanti, 2021) (Sok Yen et al., 2021). The reduction of channels opening decreases glucose entering, and consequently, the levels of blood glucose as well. The combination of these three effects gives an effective antidiabetic treatment. However,� the main drawback is the multiple molecule interactions that flavonoids can have with other compounds due to their chemical structure, producing additional non desired effects (Cahyana & Adiyanti, 2021).

Based on previous information, several researches propose that fig extracts have hypoglycemic potential to create new antidiabetic treatments (Priyoherianto & Saputra, 2018). Clinical trials results evidence that fig-leaves/fruit-derived extracts reduce the amount of glucose levels in blood, which ensures health and homeostasis in diabetic patients (Gupta et al., 2022). Moreover, several studies propose flavonoids as the components responsible of the antidiabetic, anti-inflammatory and antioxidant activity (Cahyana & Adiyanti, 2021) (Juc� et al., 2020). Three antidiabetic mechanisms are mentioned as therapeutic effects of Ficus Carica being the inhibition of digestive enzymes (α-amylase and α-glucosidase), the reduction of starch hydrolysis by creating �starch resistant molecules� and blocking the use of glucose co-transporters (Cahyana & Adiyanti, 2021) (Sok Yen et al., 2021). All of them achieve the reduction of blood glucose levels in diabetic patients.

In the case of side effects, fig extracts are better than commercial antidiabetic drugs, showing few or null side effects. Hence, they are safety for patients� health. In the same way, other profitable pharmaceutical effects have appeared during trials like hepatoprotection and decrease of cholesterol in rats (P�rez et al., 2000). These properties can support diabetic patients, reducing risks of heart attacks and cerebrovascular diseases. Also, it can be used as supplementary treatment to support commercial ones. So, diabetic patients could decrease chemical antidiabetic drugs dosage uptake, and consequently, reduce side effects, and acquire additional cardiovascular benefits.

2. Conclusion.

Ficus Carica, commonly known as �fig�, is a tree that belong to Moraceae family. It has several nutritive and pharmaceutical properties, becoming one of the most used medicinal plants worldwide. Structurally, it presents numerous spreading branches, pear-shaped fruit, milky latex and papaya-like leaves. All plant structures are used to obtain several molecules with potential pharmacological effects. Some examples are phytosterols, amino acids, anthocyanins, organic acid, among others. Usually, based on traditional medicine, fig is used to treat endocrine, respiratory, gastrointestinal and reproductive affections. Also, it can contribute with antioxidant, anticancer, cytotoxic, anti-inflammatory and hypolipidemic effects. In this review, the main pharmacologic effect studied was antidiabetic potential. When fig extract was used to treat type II diabetes, blood glucose levels decreased. Compared to chemical drugs like Metformin and Glibenclamide, fig extract shows similar antidiabetic effects. However, fig-derived treatment needs more concentration per dose to achieve similar effects as commercial treatments. By contrast, natural fig treatment presents less, or null side effects compared to chemical ones. Therefore, fig is an excellent source to obtain antidiabetic compounds to create new antidiabetic treatments because they can produce less side effects at high dose treatment concentration, having a similar effect like chemical therapies.

3. Future research and perspectives.

This review analyzes the antidiabetic potential of several compounds of fig extracts to be used as phytotherapy to treat type II diabetes. In future opportunities, the study of new applications of fig extracts can be performed, focused on diabetes during pregnancy or diabetes in animals because this natural treatment could be well tolerated by pregnant women and pets compared to commercial drugs.�

Author contributions

All the authors contributed to the development of this project.

Conflict of interest

None

 

 

 

 

 

 

 

 

 

 

 

 

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