Antidiabetic Potential Orchids: A Promising Avenue for Diabetes Mellitus Management

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Narola Jamir , Debashree Devi , Temsumayang Imchen , Wezotsho Puro , Kaushik Borah , Thejavitsu Noah Vupru , Chitta Ranjan Deb

Department of Botany, Nagaland University, Lumami-798627, Nagaland, India

Corresponding Author Email: debchitta@gmail.com

DOI : https://doi.org/10.51470/APR.2026.05.01.01

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1. Introduction

Diabetes mellitus is one of the leading and prominent metabolic disorder with a myriad of aetiologies that include chronic hyperglycaemia and abnormality in the carbohydrate metabolism by the human body, besides of carbohydrates, fats etc. due to lower blood insulin level or insensitivity of targeted organs to insulin [1]. In today’s fast-paced and sedentary world, diabetes has become a significant health concern, impacting individuals of all ages and socioeconomic backgrounds. Moreover, it poses significant challenges to healthcare systems and individuals as they strive to manage and control the disease [2]. As the prevalence of diabetes continues to rise, research into alternative treatments and potential sources of antidiabetic compounds becomes increasingly crucial. In recent years, the potential of medicinal plants, including orchids, has gained significant attention due to their unique bioactive compounds.

Facts and figures reported in the latest 2021 edition of Diabetes Atlas released by the International Diabetes Federation have shown that the current global diabetic population of 536.6 million will be augmented to a staggering number of 783.2 million by 2045 [3].

2. Classifications of Diabetes Mellitus

            Diabetes mellitus is a multifaceted, chronic metabolic condition that poses a significant global health challenge due to its rising incidence and associated severe complications. Broadly, the disease is categorized into three distinct types.

Type 1 diabetes

            Type I diabetes, historically known as insulin-dependent diabetes, arises from a severe deficiency in insulin production. This is primarily caused by the loss of functional pancreatic beta cells, often resulting from an autoimmune response where the body’s immune system erroneously targets insulin-producing cells [4]. Consequently, individuals with this condition rely entirely on exogenous insulin administration to regulate blood glucose. Clinical onset typically occurs during childhood or early adolescence. While the precise etiology of this autoimmune disorder remains elusive, factors such as genetic predisposition, family history, dietary habits, sedentary behavior, and chronic pancreatitis are believed to precipitate its development [5].

            Mechanistically, Type 1 diabetes is characterized by the immune-mediated destruction of pancreatic beta-cells by macrophages, as well as CD4+ and CD8+ T cells. Islet cell antibodies—specifically those targeting glutamic acid decarboxylase (GAD) within $\beta$-cells—are detected in approximately 85% of patients. This destruction leads to insulin deficiency and metabolic dysregulation, further compounded by the dysfunction of pancreatic $\alpha$-cells, which secrete excessive glucagon. Furthermore, unchecked lipolysis results in elevated free fatty acids, while reduced expression of hepatic glucokinase and GLUT-4 in adipose tissue impairs insulin sensitivity in target organs [6].

Type 2 diabetes

            Type II diabetes (insulin-independent) is the most prevalent form of the disease, accounting for approximately 90% of the diabetic population. In this scenario, patients either fail to produce sufficient insulin, or their bodies are unable to utilize it effectively to maintain glycemic control. The condition is often exacerbated by comorbidities such as obesity, hypertension, hyperlipidemia, and cardiovascular disease [7]. T2DM is strongly linked to sedentary lifestyles, which contribute to chronic systemic inflammation characterized by proinflammatory markers including IL-6, CRP, TNF-$\alpha$, and IL-1. Notably, IL-1 plays a critical role in the autoimmune aspect of the disease by activating the NF-kappaB transcription factor, which suppresses $\beta$-cell function and induces apoptosis [8]. Consequently, management strategies primarily focus on dietary modifications, physical activity, and pharmacotherapy [9].

Although traditionally an adult-onset condition, T2DM is characterized physically by a combination of insulin resistance and impaired insulin secretion due to $\beta$-cell degradation [10]. At the cellular level, Mitochondria-associated membranes (MAMs), responsible for lipid exchange and calcium signaling, contain key insulin signaling proteins; their dysfunction is a significant contributor to peripheral insulin resistance [6]. Additionally, microRNAs (miRNAs), which regulate various cellular processes, have been implicated in the pathogenesis of T2DM and are being investigated as potential biomarkers [11].

Gestational diabetes

The third category, gestational diabetes, is specific to pregnancy. It manifests as hyperglycemia in expectant mothers and affects approximately 7–10% of pregnancies globally [12].

3. Chronic Complications Associated with Diabetes

Diabetes mellitus is associated with a range of long-term physiological sequelae, including neuropathy, nephropathy, retinopathy, dyslipidemia, and various cardiovascular disorders [13]. These complications significantly diminish the quality of life and increase mortality rates among diabetic populations.

Cardiovascular and macrovascular pathologies: cardiovascular disease (CVD) remains a primary cause of morbidity in diabetic patients. Persistent hyperglycemia causes extensive damage to the vascular endothelium, accelerating the development of atherosclerosis. This process leads to the accumulation of arterial plaque, resulting in narrowed and hardened vessels that impede blood flow and heighten the risk of myocardial infarction and stroke. The management of comorbid factors—specifically obesity, hypertension, and dyslipidemia—is essential for mitigating cardiovascular risks in these patients [14].

Neurological impairment (diabetic neuropathy): Prolonged exposure to elevated blood glucose levels often results in diabetic neuropathy, characterized by widespread nerve damage. While this can affect various systems, it most commonly manifests in the distal extremities. Patients frequently experience a loss of tactile sensation, which increases the risk of undetected injuries, potentially leading to foot ulceration and, in severe instances, lower-limb amputation. Current research emphasizes the role of glycemic variability, suggesting that fluctuations in blood sugar levels are as detrimental as sustained hyperglycemia in the progression of nerve damage [15].

Renal dysfunction (diabetic nephropathy): Diabetic nephropathy is a critical complication involving the degradation of the kidney’s filtration units. Over time, high glucose levels impair the kidneys’ ability to process waste and excess fluids, which can progress to end-stage renal disease (ESRD) requiring dialysis or transplantation. Recent molecular studies have highlighted the influence of microRNAs (miRNAs) in this process; these non-coding RNAs appear to regulate the intercellular pathways responsible for renal pathogenesis, marking them as potential therapeutic targets for future interventions [16].

Ocular complications Diabetes also poses a severe threat to visual health, leading to conditions such as cataracts, glaucoma, and, most notably, diabetic retinopathy. The latter is driven by damage to the retinal vasculature and is characterized by increased vascular permeability, tissue ischemia, and pathological angiogenesis. Research has identified Vascular Endothelial Growth Factor (VEGF) as a primary mediator in the advancement of retinopathy [17]. If left unmanaged, these conditions can lead to permanent vision loss.

Immunological vulnerability and mental health: Beyond organ-specific damage, diabetes compromises the immune system, rendering patients more susceptible to bacterial and fungal skin infections, as well as recurrent urinary tract and yeast infections [18].

Furthermore, the disease imposes a substantial psychosocial burden. The rigorous demands of constant glucose monitoring, strict dietary adherence, and medication schedules can lead to chronic stress, anxiety, and clinical depression. This emotional strain is often compounded by the social stigma and the persistent fear of future physical complications [19].

Collectively, these complications underscore the necessity of early diagnosis, preventative strategies, and integrated management. Ongoing research into the molecular underpinnings of these pathologies is vital for curbing the global progression of diabetes and its associated burdens.

4. Drawbacks of synthetic drugs in diabetes treatment

Current medications environ an extensive variety of conventional synthetic drugs such as biguanides, α-glucosidase inhibitors (AGIs), thiazolidinediones, sulfonylureas and non-sulfonylureas secretagogues. The commonly used biguanide is metformin, which reduces hepatic glucose generation in the presence of insulin. α-glucosidase is an enzyme that breaks down complex carbohydrates into simpler forms. By inhibiting them, the AGIs slow down the uptake of carbohydrates and thus reduce postprandial blood sugar levels. Thiazolidinediones increase the uptake of glucose in the muscles and adipose tissues. Orally administered class of drugs, sulfonylureas and non-sulfonylureas secretagogues bind to receptors in the beta cells, allowing the closure of potassium adenosine triphosphate (K_ATP) channels and entry of calcium into the cell, which in turn releases insulin [20].

Regardless of their effectiveness, synthetic drugs come with several drawbacks apart from limitations like cost effectiveness, ease of availability and toxicity. Firstly, they often have side effects on prolonged usage that can range from mild discomfort to severe complications such as osteoporosis, obesity, hypoglycaemia, lactic acidosis, peripheral edema and abdominal discomfort [13]. Additionally, the continued use of synthetic drugs may lead to drug resistance, requiring high doses or alternate medications for treatment. Moreover, these drugs only manage the symptoms of diabetes and do not address the underlying cause of the disease. Therefore, the search for newer natural herbal drugs which are easily available, cost-effective, biologically safe and which do not require laborious pharmaceutical processes is desired as an alternative [21].

5. Botanical Sources as Alternative Therapeutics for Diabetes Mellitus

            Since antiquity, botanical sources have provided a foundational basis for therapeutics, with numerous traditional medicinal systems highlighting the potent antidiabetic properties of various plant species. Ethnomedical practices have leveraged these natural properties for centuries to regulate and manage glucose levels [22]. Such usage is extensively documented across diverse global cultures, most notably in India [23, 24]. Historically, the Indian subcontinent has a rich legacy of utilizing indigenous botanical remedies for diabetes, with records dating back to the 6th century BC in the foundational texts of Charaka and Sushruta [25].

            Phytochemical Composition and Mechanisms of Action The antidiabetic efficacy of medicinal plants is derived from a complex array of bioactive secondary metabolites, including terpenoids, saponins, flavonoids, carotenoids, alkaloids, and glycosides [26]. These phytoconstituents operate through multiple physiological pathways:

• Flavonoids: These compounds have been shown to facilitate cellular glucose uptake, stimulate insulin secretion, retard glucose absorption within the gastrointestinal tract, and inhibit key enzymes responsible for endogenous glucose production.
• Alkaloids: These molecules demonstrate significant hypoglycemic effects by enhancing insulin sensitivity and optimizing glucose metabolic pathways.

            Beyond their biochemical efficacy, medicinal plants offer strategic advantages over synthetic pharmacological agents. They are often more accessible and cost-effective, particularly in regions where conventional pharmaceutical infrastructure is limited [27]. Pharmacological and ethnobotanical scope extensive research, ranging from ethnobotanical surveys to rigorous pharmacological evaluations, continues to identify promising compounds for diabetes management. It is estimated that between 800 and 1,200 plant species possess inherent antidiabetic potential. A significant number of these have already demonstrated measurable bioactivity when subjected to modern experimental validation [28].

6. Orchids and Diabetes: A Comprehensive Overview

            The Orchidaceae family is among the most expansive and diverse groups of flowering plants, comprising an estimated 25,000 to 35,000 species [29]. While widely celebrated for their ornamental and aesthetic appeal, orchids have increasingly become a focal point for pharmacological research due to their unique ecological adaptations and specialized secondary metabolites [30]. Beyond their horticultural value, members of the Orchidaceae family are recognized for significant antidiabetic properties [31]. This vast genetic diversity provides a rich reservoir for the discovery of novel bioactive compounds. Historical records indicate that Chinese traditional medicine was the first to document the therapeutic utility of orchids, many of which are now the subjects of rigorous phytochemical and pharmacological investigation [32].

            India serves as a primary biodiversity hotspot for orchids, hosting approximately 2,500 species across 167 genera. Despite this abundance, the full therapeutic potential of Indian orchids remains underutilized due to a lack of comprehensive scientific validation and a limited understanding of their molecular mechanisms. There is an urgent need for standardized clinical research, the development of robust bioassays, and thorough toxicological evaluations using various animal models to ensure safety and efficacy [9]. Although the application of orchids in modern diabetes treatment is in its early stages, preliminary studies have demonstrated significant hypoglycemic activity, suggesting a promising role for these plants in managing hyperglycemia.

• Bioactive constituents and molecular mechanisms

            Orchids synthesize a diverse array of secondary metabolites that underpin their medicinal efficacy. These include phenols, flavonoids, alkaloids, tannins, steroids, phenanthrenes, stilbenoids, and various glycosides [33]. Many of these compounds have exhibited potent antidiabetic effects in both in vitro and in vivo models [34][33][34][35][36] [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]. Some of the key molecules are listed here: Alkaloids: Molecules such as dendrobine, erianin, and gigantol have shown efficacy in lowering blood glucose and mitigating diabetic cataracts; Stilbenoids: Thunalbene (3,3′-dihydroxy-5-methoxystilbene), first isolated from Thunia alba, possesses antioxidant, anti-inflammatory, and antidiabetic properties [33]; Gigantol: Found in Dendrobium species, it exhibits a broad pharmacological profile, including neuroprotective, vasorelaxant, and anti-cataractogenic activities [52]; Kinsenoside: Extracted from Anoectochilus roxburghii, it facilitates the restoration of pancreatic $\beta$-cells and regulates antioxidant enzymes to combat oxidative stress [34].

            A primary mechanism for these effects is the reduction of oxidative stress and insulin resistance [53]. Chronic hyperglycemia triggers the overproduction of reactive oxygen species (ROS), which damages beta-cells and exacerbates insulin resistance. Furthermore, elevated glucose leads to the formation of Advanced Glycation End-products (AGEs). Antioxidant compounds found in various orchid species neutralize these free radicals, thereby improving insulin sensitivity and protecting cellular integrity [36][38][39][40][54][55][56][57][58] [59][60][61][62][63][64][65].

6.2 Conservation status

            The surge in demand for medicinal orchids has led to unsustainable harvesting and significant depletion of wild populations. Habitat loss due to deforestation and urbanization further threatens these species. Consequently, many orchids are listed on the IUCN Red List of threatened species, and the entire Orchidaceae family is protected under Appendix II of CITES to regulate international trade [66].

6.3 Ethnomedicinal and pharmacological perspectives

            A systematic literature review was conducted using databases such as Google Scholar, Science Direct, and PubMed Central to evaluate the antidiabetic potential of orchids. Ethnobotanical data reveals that 44 to 50 orchid species across 21 genera are traditionally employed to treat diabetes (Table 1). The genus Dendrobium is the most well-represented, with species like D. officinale being a staple in nearly 190 polyherbal formulations in China [74, 75]. Other notable genera include Anoectochilus, Eulophia, and Dactylorhiza, used across India, Thailand, Turkey, and Africa [28][59][79][80].

• Pharmacological mechanisms of action

Pharmacological evidence (summarized in Table 2) identifies several key pathways through which orchids exert antidiabetic effects:

I. Digestive enzyme inhibition: Species such as Dactylorhiza hatagirea and Dendrobium polyanthum inhibit $\alpha$-amylase and alpha-glucosidase, slowing carbohydrate digestion and reducing postprandial glucose spikes [32][79][94][95].

II. Antioxidant defense: Phenolics and polysaccharides from Acampe praemorsa and Gastrodia elata scavenge free radicals (DPPH, hydroxyl), preventing lipid peroxidation and protecting vital tissues [46][49][104].

III. Insulin signaling and islet protection: Extracts from D. candidum and D. officinale stimulate insulin secretion, promote beta-cell regeneration, and enhance insulin signaling via the AKT phosphorylation pathway [34][106][111].

IV. Glucose uptake and GLUT4 modulation: Orchids like Anoectochilus burmannicus and D. loddigesii upregulate GLUT4 expression, facilitating the transport of glucose into adipose and muscle tissues [62][113][114].

V. Anti-inflammatory activity: Orchid-derived compounds attenuate low-grade systemic inflammation by modulating cytokines like TNFα and CRP, thereby reducing insulin resistance [53][62][115].

VI. Hypolipidemic and hepatoprotective effects: Species like D. nobile regulate lipid metabolism by downregulating lipogenesis genes (e.g., Srebp1), reducing triglycerides, and improving hepatic function [106][108][116].

VII. Anti-AGE activity: D. brymerianum and Prosthechea michuacana prevent the glycation of proteins, which is critical in avoiding long-term vascular and neural complications [60][96][118].

VIII. Targeted organ protection: Nephroprotective: D. officinale preserves glomerular structure and improves renal biomarkers [107]; Retinoprotective: D. chrysotoxum and erianin inhibit VEGF expression to maintain the retinal barrier [43][48]; Cardioprotective: Polysaccharides mitigate diabetic cardiomyopathy by reducing oxidative stress [75]; Gut microbiota modulation: Recent evidence suggests D. aphyllum enhances beneficial microbial diversity and short-chain fatty acid (SCFA) production, aiding glucose metabolism [110]; Anti-obesity effects: Species like D. delacourii inhibit adipogenesis and reduce lipid accumulation, addressing a core risk factor for Type 2 Diabetes [53][97][120].

7. Constraints in the Development of Orchid-Based Antidiabetic Agents

            Despite their therapeutic promise, the transition of orchids from traditional remedies to mainstream pharmaceutical agents faces several significant bottlenecks [121]. These challenges can be categorized into logistical, ecological, and regulatory domains.

I. Logistical and cultivation barriers: The commercial-scale production of orchids for drug development presents immense logistical hurdles. Orchid cultivation is notoriously labor-intensive and time-consuming, often requiring precise environmental control over temperature, humidity, and light—factors that make artificial propagation both complex and expensive [122, 123]. Furthermore, many species with high antidiabetic potential are endemic to remote, biodiversity-rich regions. Geographic barriers, political instability, and underdeveloped infrastructure in these areas often impede researchers’ ability to secure sufficient samples for comprehensive study.

II. Ecological and conservation concerns: The extraction of bioactive compounds from wild orchids poses a direct threat to natural ecosystems. Orchids are highly sensitive to habitat loss caused by deforestation, climate change, and illicit harvesting [124]. With many species already classified as endangered, conservation is a critical priority. Responsible utilization necessitates the development of sustainable harvesting protocols and a commitment to preserving natural habitats [125].

III. Scientific and regulatory hurdles: The pathway to clinical approval is demanding. There is currently a significant disparity between folkloric reports and rigorous scientific validation. Specific data regarding the isolation, safety, and efficacy of individual bioactive compounds remain sporadic, and human clinical trials are virtually non-existent [28]. Additionally, the complex regulatory landscape—encompassing ethical considerations and the requirements for standardized clinical application—often deters pharmaceutical investment, thereby slowing the commercialization of orchid-derived treatments.

To bridge these gaps, several strategies are recommended: I. Biotechnological alternatives: Leveraging tissue culture and synthetic biology can facilitate the production of bioactive compounds without depleting wild populations [123]; II. Conservation advocacy: Implementing education campaigns and establishing protected areas can ensure the survival of valuable species while supporting research [107] and III. Streamlined regulation: Enhancing collaboration between researchers and regulatory bodies could optimize the approval process for plant-based therapies without compromising safety standards.

8. Conclusion

            The emerging interest in the antidiabetic properties of orchids represents a significant opportunity for pharmacological innovation. Intensified research into the bioactivity and molecular mechanisms of these plants is essential to unlock their full potential as targeted therapeutic agents. By integrating these natural compounds into modern medicine, we may reduce the current reliance on synthetic pharmaceuticals and move toward a more integrated, holistic approach to diabetes management. While the journey from “nature’s pharmacy” to the clinical setting requires extensive validation through rigorous trials, the exploration of orchids underscores the vast, untapped potential of botanical resources. Continued investigation into this diverse family may yet yield critical breakthroughs for global health and well-being.

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