A Review of Ethnobotanical Perspectives on Diabetes: Comparative Phytopharmacology of Limonia acidissima L. and Bauhinia vareigata.L.

The rapid growth of cities and modernization has significantly changed our ways of life, leading to poor dietary choices, lack of physical activity, increased levels of stress, and greater exposure to negative environmental factors. These changes contribute to the global increase in obesity and type 2 diabetes mellitus (DM). (Preethi Chandrasekaran et al., 2024).  Approximately 537 million adults worldwide suffer from diabetes (2021). By 2030 and 2045, that number is predicted to increase to 643 million and 785 million, respectively.             Insulin resistance, which is characterized by decreased insulin efficacy in the liver and decreased glucose absorption in skeletal muscle and adipose tissue, is brought on by obesity. Four major metabolic abnormalities are commonly seen in people with diabetes: increased endogenous glucose synthesis, decreased insulin secretion, faulty insulin action, and excess adiposity. (Huiqin Guo et al.,2023).  In the Political Declaration on the Prevention and Control of Noncommunicable Diseases (NCDs), diabetes is included as a priority aim along with cancer, chronic respiratory conditions, and cardiovascular disease (CVD). (Gojka Roglic, 2016). The burden of diabetes, including instances that go misdiagnosed and untreated, is increasingly being borne by low- and middle-income nations. (Majid Ezzati 2024).  In these areas, where access to screening, management, and preventative measures frequently lags, this disproportionate burden puts a strain on healthcare systems and economies. Multifaceted approaches are needed to address these interrelated issues, such as improved opportunities for physical exercise, nutritional education, and regulatory changes to support healthier urban environments. (Felicia Hill-Briggs et al.,2023).  Insulin resistance development and metabolic consequences can be mitigated by early detection and intervention, highlighting the need for global health initiatives adapted to settings with low resources. (Marc Gregory Yu et al., 2024).

1.1 Diabetes Mellitus Overview:

Persistent hyperglycemia brought on by deficiencies in insulin secretion, action, or both characterizes diabetes mellitus (DM), a chronic metabolic disease. Pancreatic beta cells produce insulin, which controls blood sugar levels. Diabetes mellitus (DM) causes both immediate and long-term problems because the body is unable to properly manufacture or use insulin. Due to its high rates of morbidity, mortality, and expenses, DM presents significant worldwide health issues. (Ahmed Abdelhalim Yameny 2024).

2.Types of Diabetes:

The autoimmune death of pancreatic beta cells, which stops the synthesis of insulin, is the cause of type 1 diabetes. If left untreated, symptoms can develop abruptly, frequently within months, and cause fast hyperglycemia that could harm organs. (R Roy et al., 2023).  Insulin resistance in tissues, beta-cell malfunction, and decreased insulin production lead to type 2 diabetes. Obesity, high blood sugar, hypertriglyceridemia, poor diet, inactivity, aging, family history, stress, and mental health problems are important risk factors. Metformin, other glucose-lowering medications, changes to their lives, and sometimes insulin are all part of management. (Oluwafemi Adeleke Ojo et al., 2023). Glucose intolerance initially identified during pregnancy is known as gestational diabetes mellitus (GDM). Complications include macrosomia, shoulder dystocia, birth trauma, preterm, perinatal mortality, and caesarean delivery are more likely to occur. Mothers with GDM are also more likely to create type 2 diabetes and cardiovascular disease in the future; pre-pregnancy variables may increase the risk and have an impact on the kids.  Blood glucose levels over normal but below diabetic criteria are known as prediabetes. It shows an increased risk of diabetes mellitus, which is often reversible with lifestyle changes. (Samar A. Antar et al., 2023).

Figure 01 Pathophysiology of Diabetes Mellitus: (Nushrat parveen et al., 2017

3 Common Symptoms (Type 1 and Type 2):

• An increase in hunger and thirst
• Urinating a lot
• Exhaustion and agitation
• Weight loss that is not explained
• Vision blurriness
• Slow-healing injuries
• Polyuria
• Polydipsia
• Polyphagia
• Numbness or tingling in the hands or feet
• Regular infections (skin, for example) (Moxinur Maxmudova Ne’matillayevna 2025)

     Diagnostic Tests :

• The average blood glucose over a period of two to three months is measured by hemoglobin A1c (HbA1c). Diabetes is indicated by ≥6.5%, which is helpful in determining risk and consequences.
• After an 8-hour fast, fasting plasma glucose (FPG) is measured; ≥126 mg/dL indicates diabetes.
• Random Plasma Glucose: Taken after a meal at any time. Diabetes is indicated by ≥200 mg/dL with symptoms.
• After a glucose load, the Oral Glucose Tolerance Test (OGTT) gauges glucose clearance. mostly used for GDM and type 2 diabetes screening. C-peptide : Helps distinguish between different types of diabetes by measuring blood and urine levels to evaluate beta-cell activity. (Oluwafemi Adeleke Ojo et al., 2023).
• Autoantibodies: Confirms the autoimmune origin of type 1 diabetes by identifying markers such as insulin autoantibodies or anti-GAD. (Addissouky, Tamer A. et al., 2024)
• Wearable electrochemical sensors are non-invasive devices that track biomarkers and glucose in interstitial fluid, sweat, or saliva. They can be integrated with cloud storage and apps. (Tamoghna Saha et al., 2021).

4 Table 1. Roles of different conventional targets in diabetes mellitus: (Roni Weinberg Sibony et al., 2023)

Figure 2. The number of Americans with diabetes is expected to change in 2010, 2025, and 2050. The adjustments imply that the prevalence of diabetes will rise steadily from 3.99% in 2000 to 7.21% in 2050, that the population will continue to expand from 275 million in 2000 to 404 million in 2050, and that demographics will shift, with the highest increases occurring in the oldest age group and among Black people. The majority of the growth is anticipated to be due to shifting demographics. (Nathaniel Winer et al., 2004).

5. Complications Associated with Diabetes Mellitus (DM):

The "Standards of Care in Diabetes" published by the American Diabetes Association (ADA) include important aspects of diabetes care, treatment objectives, and methods for evaluating the quality of care. (Diabetes Care 2026). Both macrovascular outcomes, such as myocardial infarction (MI), stroke, lower limb arteriopathy, and cardiovascular mortality, and microvascular complications, such as treatment-induced neuropathy, retinopathy, renal dysfunction, and Charcot's neuroarthropathy, are impacted by intensive and quick correction of hyperglycemia. (Juliana Poonoosamy et al., 2023). Cognitive dysfunction, including dementia, diminished verbal memory, attention problems, and deficiencies in executive function, affects 13–24% of individuals with diabetes. Type 1 diabetes (T1D) is linked to autoimmune thyroid illness, Addison's disease, rheumatoid arthritis, and celiac disease. Type 2 diabetes (T2D) is linked to Alzheimer's disease, pancreatic cancer, Cushing's syndrome, and polycystic ovarian syndrome (PCOS). (Samar A. Antar et al., 2023). Important risk factors and correlations include the micronutrient iron and macronutrients that raise the risk of type 2 diabetic mellitus (T2DM). (Alexandria V. Harrison et al., 2023). Diabetes is the primary cause of end-stage renal disease in Western nations and is associated with high rates of cardiovascular events. (David B. Sacks et al., 2023). T2D risk is influenced by lifestyle and environment, although among people between the ages of 35 and 60, heritability is predicted to be 69%. (Andrew Morris et al. 2023). Elderly people are more likely than middle-aged people to have prediabetes (55.2%) and diabetes (15.9%), with age being a major risk factor. (Zihui Yan et al., 2023).

6 Protein Glycation and Advanced Glycation End Products (AGEs):

The interaction between sugars and amino acids produced a series of brownish compounds, which Louis-Camille Maillard originally reported in 1912. Maillard chemistry, which aims to comprehend the intricate web of reactions that take place when amino acids or proteins are combined with hydroxy aldehydes or their oxidation byproducts (mostly α-oxo-aldehydes), was born at that time. The majority of scientists in Maillard's profession concentrated their efforts between 1912 and about 1970 on trying to comprehend how these reactions were able to provide foods and beverages flavor and taste, as their understanding could aid to improve their organoleptic properties. Concurrently, it was found that the Maillard reaction took place in the majority of industrial heating procedures, including those utilized in the textile industry. (Trézl et al., 1997; Ohe and Yoshimura, 2014), cosmetic (Fusaro and Rice 2010), or biopharmaceutical industries. (Ana Belén Uceda et al., 2024) Complications from chronic diabetes lead to substantial public health expenses, mortality, and disability. A key role is played by heterogeneous molecules known as advanced glycation end products (AGEs), which are produced when proteins, lipids, and nucleic acids undergo non-enzymatic glycation and oxidation. Hyperglycemia, oxidative stress, and extended protein/lipid turnover all hasten the development of AGEs. AGEs cause insulin resistance in peripheral tissues and impair pancreatic β-cell function by directly crosslinking proteins or binding receptors such as RAGE (full-length RAGE). (Qimou Chen et al., 2024). In euglycemic conditions, the generation of AGEs progresses slowly; however, in hyperglycemia, oxidative stress, and circumstances involving extended protein and lipid turnover, it accelerates. By attaching to advanced glycation product receptors (RAGE), often referred to as full-length RAGE (Fl-RAGE) on the cell surface, AGEs can either directly grab and crosslink proteins or activate signalling cascades, resulting in peripheral tissue insulin resistance and reduced pancreatic β-cell function.

6.1 Historical Overview of Glycation:

 Glycation chemistry has been around for more than a century. In 1912, the Maillard reaction caused "browning" when amino acids were heated with glucose. Amadori and Heyns rearrangements, which convert aldose or ketose sugars into stable α-ketoamines, are important processes. Glycation is linked to neurodegeneration and aging in addition to metabolic diseases. Alzheimer's patients' cerebrospinal fluid contains higher methylglyoxal-hydroimidazolone (MG-H1) adducts, which may be caused by cytoskeletal crosslinking that impairs neuronal function. (Marissa N .Trujollo, 2023). Every living thing that has been studied thus far has protein glycation. This widespread, low level of glycation points to a perhaps more extensive physiological role that is essential to cell survival and balance. To prepare cells for times of elevated glycolytic flux and exposure to glycating substances (like hormesis), they may need to be exposed to low, basal levels of protein glycation. Therefore, we believe that glycation plays a significant role in metabolic homeostasis at low levels.

Figure 3. Steps involved in formation of AGEs:

6.2 Molecular Mechanisms of Protein Glycation:

Glycation starts when the carbonyl of glucose combines with the main amino group of a protein (N-terminal α-amino or Lys ε-amino) to generate a reversible Schiff base (open-chain aldimine equilibrating to stable glycosylamine). This gradually reorganizes into a stable ketoamine (product of Amadori). The Amadori rearrangement typically entails an acid-catalyzed ring opening of glycosylamine to produce an iminium ion, which subsequently deprotonates to form a 1,2-enaminol in equilibrium with the Amadori product. While the creation of an Amadori product is slower but thermodynamically more favored, the formation of a Schiff base is comparably quick and highly reversible. Reactive carbonyl species (RCS) production and protein carbonylation are the two phases of AGE growth. (Yanchi Chen et al. 2024). By generating pro-inflammatory cytokines, aberrant proteins and growth factors, altered extracellular matrix (ECM), and reactive oxygen species (ROS), AGEs damage tissues. (Katarzyna Zgutka et al., 2023).

Figure 4. Molecular mechanism of Protein Glycation:

Plants and Antidiabetic Properties:

Both traditional use and contemporary study have demonstrated the antidiabetic properties of some medicinal herbs. For instance, the anti-hyperglycemic medication metformin, which is currently used extensively to treat type 2 diabetes, is derived from chemicals found in Galega officinalis, or goat's rue, which was once used for similar purposes. (Clement G. Yedjou et al., 2023).

Table 2. Other Plants for Diabetic Treatment found Tirupati District: (Ebenezer Kwabena Frimpong et al., 2024)

7 Prevalence of Diabetes:

Over the past 40+ years, both in the US and worldwide, the prevalence of diabetes has increased dramatically. Important past and future trends include: (Bin Zhou et al., 2024).

Table 3. Global Trends:

• Update: According to the IDF Diabetes Atlas, actual numbers for 2021 were 537 million adults; India currently has about 77 million cases, and by 2045, that number is expected to rise to 134 million.

• US Trends: In the early 2000s, there were about 17 million confirmed cases and 5.9 million undiagnosed cases. 29 million people were predicted to be diagnosed by 2050 based on trends from 1980 to 1998. 38.4 million (11.6% of adults), with around 9 million undiagnosed, according to CDC data from 2025.

Type 2 diabetes drives most of the increase, linked to aging populations, obesity, and urbanization.

8 Limonia acidissima L.

It is a well-known native fruit of India that is a member of the Rutaceae family and is also referred to as Bael. The globose fruit of the subtropical deciduous Bael fruit tree has a hard, woody shell that is either grey or yellowish. There are numerous seeds and a delicate golden or orange mucilaginous flesh inside. You can even eat these raw. Wood apples are used in jujubes, candies, juice, sauce, and other value-added products. [Singh, S. et al., 2024].

8.1 Name & Synonyms:

Scientific name: Limonia acidissima L.
Synonyms: Feronia elephantum, Feronia limonia, Schinus limonia. (Salema Khatun et al., 2024)
8.2 Vernacular names (India):

• English: Wood apple, Elephant apple

• Hindi: Kaitha / Kathbel

• Sanskrit: Kapiththa

• Telugu: Velaga pandu / Velaga

• Tamil: Vilampazham / Vilam

• Kannada: Belada hannu / Belada mara

• Malayalam: Vilam

• Marathi: Kavath / Kaitha

• Gujarati: Kavath

• Bengali: Kodbel / Kathbel

• Odia: Kaitha

• Punjabi: Kaitha

• Assamese: Thekera / Kathbel (Swati M. Wakchoure et al., 2023)

8.3 Taxonomical Classification:

• Kingdom: Plantae
• Division: Magnoliophyta
• Class: Magnoliopsida
• Order: Sapindales
• Family: Rutaceae
• Genus: Limonia
• Species: L. acidissima (A. R. Sowjanya et al., 2025)

8.4 Geographical Distribution:

Native to South Asia (India, Pakistan, Bangladesh, Sri Lanka); cultivated or naturalized in Southeast Asia. (Varsha C et al., 2023).

8.5 Cultivation and Collection:

It thrives in hot, dry tropical climates and requires sandy or loamy soil that drains well. The plant is grown from seeds, which typically sprout in two to three weeks. Ripe fruits are used to harvest seeds, which are then planted in the field after 6 to 8 months. Plants are typically spaced 8 to 10 meters apart, require minimal water once they are mature, and begin to bear fruit after 5 to 7 years. Fruits are often picked when they are fully ripe but not yet overripened. Fruits are gathered, When the fruits are totally mature, gather them. Ripe fruits have a brown shell and are firm. Fruits are manually plucked, the pulp is separated, dried, or preserved once the hard shell is physically cracked.   

Figure 05 : Limonia Acidissima L

8.6 Morphology:

• Habit: Deciduous tree, 9–20 m tall, with rough, spiny bark.
• Leaves: Pinnate, 5–7 leaflets; lemon scent when crushed.
• Flowers: Small, white to pale yellow, five-petalled.
• Fruit: Hard-rinded berry, 5–9 cm diameter, brownish green; sticky brown pulp with small seeds.

Table 4.  Different parts used  in Limonia acidissima L and extraction:

8.7 Active Phytoconstituents:

Flavonoids, sometimes referred to as polyphenols, are phytochemical compounds that are present in a wide variety of plants and herbs and are crucial antioxidants that combat free radicals. However, flavonoids are rapidly and abundantly excreted through the process of urine excretion in the human digestive system, with very little absorption occurring in the intestine. [G. Williamson et al., 2018]. The primary constituents of essential oils are terpenoids, which have been shown to have anticancer, antibacterial, anti-inflammatory, antioxidant, and anti-allergic properties. [A. Masyita et al., 2021]. A secondary metabolite of phenolic substances, tannin gives L. acidissima fruit its bitter and astringent flavor. Proteins and other organic molecules that include alkaloids and amino acids can react with it and coagulate. [W. M. Oo, M. et al., 2017].

Quercetin:

2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one

Catechin:

(2R,3S)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-chromene-3,5,7-triol

Ferulic acid:

(2E)-3-(4-hydroxy-3-methoxyphenyl) prop-2-enoic acid

Kaempferol:

3,5,7-trihydroxy-2-(4-hydroxyphenyl) chromen-4-one

Gamma sitosterol:

(3S,8S,9S,10R,13R,14S,17R)-17-[(2R,5S)-5-ethyl-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol.

8.8 Pharmacological Properties:

Reported activities from studies:

• Hepatoprotective and antioxidant (stem bark, fruit extracts in liver injury models).
• antimicrobial and antifungal (against certain fungi and Gram-positive and Gram-negative bacteria).
• anti-diarrheal (regulation of GI motility).
• antidiabetic (insulin sensitivity, phenolics for glucose regulation, and flavonoids).
• Other: Potential anticancer, anti-inflammatory, anti-venom, anti-malarial, and anti-dysentery. (Dr.Anjana Dhakar et al., 2019
• Hexane, chloroform, and methanolic extracts from V. jatamansi rhizomes were used to investigate antibacterial activity. After being isolated from urinary tract infections, extended spectrum B-lactamase from Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, and Hafnia alvei was tested using a double disc diffusion assay with three solvent extracts. [Rekha Tarasingh Rajput 2023].

9 Bauhinia variegata L.

Bauhinia variegata L. is a genus of flowering herbs belonging to the Fabaceae family of legumes. It extends from Southeast Asia and China to the Indian subcontinent. Mountain ebony and orchid tree are common names, yet they are not related to the Orchidaceae family. It is frequently referred to as Kachnar, Kachnal, or Gurial in Pakistan. (GRIN, Agricultural Research Service. USDA 2019). indigenous people's traditional medical system. Many parts of this edible plant are used as anthelmintic, antimicrobial, anti-leprotic, astringent, liver tonic, and to cure dysmenorrhea. Additionally, skin conditions, diarrhoea, ulcers, wounds, edema, eye disorders, piles, haemorrhoids, and an antidote to snake bites can all be treated with Bauhinia variegata L. [Sidra Muhammad Ali et al., 2021].

9.1 Name & Synonyms:

Scientific name: Bauhinia variegata L.
Synonyms/varieties: Bauhinia candida, B. variegata var. Albo flava. (Shiv Kumar et al., 2020).
9.2 Vernacular names (India):

• English: Orchid tree, Mountain ebony

• Sanskrit: Kanchanara / Kovidara

• Hindi: Kachnar / Kanchan

• Telugu: Kanchanara / Mandaram

• Tamil: Mandarai / Mandaram

• Kannada: Mandara / Kanchanara

• Malayalam: Mandaram

• Marathi: Kanchan / Kachnar

• Gujarati: Kanchan / Kachnar

• Bengali: Kanchan / Rakta-kanchan

• Odia: Kanchanara

• Punjabi: Kachnar

• Assamese: Kanchan (Thakur Tanika et al., 2022)

9.3 Taxonomical Classification:

• Kingdom: Plantae
• Order: Rosales
• Family: Caesalpiniaceae
• Genus: Bauhinia
• Species: B. variegata. (Amandeep Singh et al.,2019)

9.4 Geographical Distribution:

Originally from South and Southeast Asia (India, Pakistan, Nepal, Bangladesh, China, Myanmar, Thailand), it is grown in various tropical areas. (Syeda shahana et al., 2017).
9.5 Cultivation and collection:

It develops in tropical and subtropical climates, requires well-drained loamy soil, and survives in areas with annual rainfall between 760 and 1900 mm. It avoids extremely dry areas below 500 mm, mostly through seeding. Seeds are sown in nursery beds, and seedlings are moved after four to six months. It requires moderate irrigation, and it grows more quickly than Limonia acidissima. Buds, flowers, leaves, and bark are gathered. When the plant is fully grown, the bark is gently peeled, flowers and buds are gathered during the flowering season, and plant parts are shade-dried and preserved.

Figure 06: Bauhinia variegata L.

9.6 Morphology:

• Habit: Deciduous tree, 10–15 m tall.
• Leaves: Bilobed, ovate, cleft ("camel’s foot" shape).
• Flowers: Pink to white, 5-petalled, in clusters.
• Fruit: Dehiscent pod, 20–30 cm long, with multiple seeds. (Raghuveer Irchhaiya et al., 2014).

Table 5. Different parts used in Bauhinia variegata L: (Thakur Tanika et al., 2022)

9.7 Active Phytoconstituents: 

• Flavonoids (quercetin, kaempferol, apigenin, rutin)
• Phenolic acids, polyphenols, tannins, saponins
• Sterols, triterpenoids (stigmasterol, lupeol)
• Glycosides, proteins, fatty acids
• Unique: Bauhinia statins, bauhinoxepins, bauhichamines, phenanthraquinones (bauhinione).(M. Dhavadharshini et al., 2025).

Rutin:

2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6- [[(2R, 3R, 4R, 5R, 6S)-3, 5-trihydroxy-6-methyloxan-2-yl]oxymethyl]oxan-2-yl] oxychromen-4-one

Protocatechuic acid:

3,4-dihydroxybenzoic acid

Lupeol:

(1R,3aR,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a,5a,5b,8,8,11a-hexamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-ol

9.8  Pharmacological Properties:

Reported from preclinical studies:

• Antioxidant, anti-inflammatory (flavonoids, polyphenols).
• Antidiabetic (glucose-lowering, lipid profile effects).
• Antimicrobial (bacteria, fungi).
• Hepatoprotective, nephroprotective (liver/kidney models).
• Anticancer, cytotoxic (in vitro).
• Other: Immunomodulatory, anti-arthritic, antiulcer, analgesic, antihyperlipidemic. (Kapil Gautam et al., 2023).

Table 6.  List of medicinal plants used in diabetes: