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EURASIAN EXPERIMENT JOURNAL OF MEDICINE AND MEDICAL SCIENCES (EEJMMS)
ISSN: 2992-4103
©EEJMMS Publications Volume 6 Issue 3 2025

Page | 82

The Role of Traditional Herbal Formulations in Managing

Metabolic Syndrome: Evidence from Obesity and Diabetes
Models
Nyiramana Mukamurera P.
Faculty of Medicine Kampala International University Uganda

ABSTRACT
Metabolic syndrome characterized by obesity, insulin resistance, dyslipidemia, and hypertension poses a
growing global health burden. While synthetic drugs address individual components, their side effects and often
limited holistic efficacy have revived interest in traditional herbal formulations. This review explores evidence
from in vitro, animal, and human studies on single and polyherbal preparations used to manage metabolic
syndrome, particularly obesity and type 2 diabetes. Key formulations such as F2 (a blend including Orostachys
japonica, Rhus verniciflua, Geranium thunbergii, royal jelly, and lemon juice) demonstrate multi-targeted actions:
inhibiting adipogenesis, reducing oxidative stress, and improving lipid and glucose metabolism in diet-induced
obese (DIO) mice). Polyherbal combinations containing Curcuma longa, Gymnema sylvestre, and Emblica officinalis
modulate body weight, blood pressure, glucose, triglycerides, and HDL in animal models). Clinical trials and
meta-analyses reveal that green tea, Phaseolus vulgaris, Garcinia cambogia, and Nigella sativa significantly reduce
weight, waist circumference, and triglycerides). Aloe vera and basil extracts show promise in improving insulin
resistance and lipid profiles). Mechanistically, these herbs act via appetite suppression, thermogenesis, inhibition
of lipase activity, improvement of insulin sensitivity, and antioxidative/inflammatory modulation). While
evidence is compelling, limitations such as small trials, lack of standardization, and potential herb-drug
interactions must be addressed. Future directions include well-designed RCTs, standardized formulations, and
exploration through omics approaches to enable integration of herbal therapies into mainstream metabolic
syndrome management.
Keywords: metabolic syndrome, polyherbal formulations, obesity, type 2 diabetes, traditional herbal medicine

INTRODUCTION
Metabolic syndrome (MetS) is a complex health condition characterized by a cluster of interrelated
cardiometabolic disorders that include abdominal (central) obesity, elevated fasting blood glucose, dyslipidemia
(typically high triglycerides and low HDL cholesterol), and hypertension[1–4]. These risk factors
synergistically increase the likelihood of developing chronic diseases such as type 2 diabetes mellitus (T2DM),
non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD), including heart attacks and
strokes[5–7]. The prevalence of MetS has been rising at an alarming rate globally, primarily due to the
increasing adoption of sedentary lifestyles, the widespread availability of calorie-dense processed foods, and the
growing incidence of obesity across all age groups[8–10].
Conventional medical approaches to treating MetS often involve pharmacological agents that target individual
components of the syndrome[11, 12]. For instance, antihypertensive medications manage blood pressure, lipid-
lowering drugs such as statins reduce cholesterol levels, and insulin sensitizers like metformin help control
blood glucose[13]. However, these monotherapies frequently fall short in addressing the multifactorial nature
of MetS. Treating one symptom in isolation does not necessarily alleviate the systemic metabolic dysfunction
that underlies the condition[13]. Additionally, long-term use of such medications can result in undesirable side
effects—metformin, for example, is known to cause gastrointestinal discomfort in many patients, while statins
have been associated with liver enzyme elevation and muscle pain[14]. Furthermore, the financial burden
associated with polypharmacy in chronic conditions often poses a significant challenge, particularly in low- and
middle-income countries.
In response to these challenges, there has been growing interest in complementary and integrative medicine,
especially herbal therapies, as potential alternatives or adjuncts to conventional treatment strategies. Herbal

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medicine, rooted in traditional systems such as Ayurveda, Traditional Chinese Medicine (TCM), and African
folk medicine, has been used for centuries to treat metabolic imbalances. Herbs like Azadirachta indica (neem),
Trigonella foenum-graecum (fenugreek), Cinnamomum verum (cinnamon), and Momordica charantia (bitter melon)
have long been employed to support blood sugar control, reduce inflammation, and improve lipid
metabolism[15]. These botanicals are believed to offer synergistic effects due to their multi-component nature,
targeting multiple pathways involved in MetS pathophysiology while posing relatively fewer side effects
compared to synthetic drugs[15].
Modern scientific research is increasingly validating these traditional claims. Preclinical studies using animal Page | 83
models and in vitro systems have elucidated numerous bioactive compounds within these herbs, such as
flavonoids, saponins, alkaloids, and polyphenols[15]. These compounds have demonstrated anti-inflammatory,
antioxidant, insulin-sensitizing, and lipid-lowering properties. Clinical trials have also provided promising
results, with certain herbal formulations showing significant improvements in glycemic control, blood pressure,
and lipid profiles among patients with T2DM or MetS[15, 16]. For instance, cinnamon has been shown to
improve insulin sensitivity and lower fasting blood glucose, while fenugreek seeds may aid in reducing
postprandial glucose spikes and triglyceride levels[17]. Despite the encouraging evidence, several limitations
still hinder the widespread clinical adoption of herbal therapies. Many studies have small sample sizes, short
durations, and lack standardized dosing or formulation protocols[17]. Moreover, herbal products can vary
significantly in their phytochemical composition depending on cultivation conditions, preparation methods, and
storage, which can affect consistency and reproducibility of therapeutic outcomes. Drug-herb interactions are
also a concern, especially when used concurrently with conventional medications[18]. This review aims to
provide a comprehensive synthesis of the current evidence on traditional herbal formulations used in the
management of MetS, with a particular focus on obesity and diabetes models. It will explore their therapeutic
potentials, mechanisms of action, limitations, and challenges in clinical translation. Additionally, it will highlight
the importance of rigorous scientific validation, standardization, and regulatory oversight to facilitate the
integration of effective herbal therapies into mainstream healthcare. Future research directions will also be
discussed, including the need for large-scale randomized controlled trials and the application of systems biology
and network pharmacology to unravel complex herb-drug interactions and optimize formulation efficacy.
Herbal Extracts & Formulations: Preclinical Evidence
F2 Polyherbal Formulation in DIO Mouse Model
The F2 polyherbal formulation represents a carefully standardized blend of ethanol extracts derived from five
biologically active components[19]: Orostachys japonica, Rhus verniciflua, Geranium thunbergii, lemon juice, and
royal jelly. This combination was specifically evaluated in a diet-induced obesity (DIO) mouse model to
investigate its anti-obesity and metabolic regulatory effects[19]. Initially, mice were fed a high-fat diet (HFD)
for five weeks to reliably induce obesity and mimic metabolic syndrome characteristics commonly observed in
humans. Following obesity induction, the animals received oral administration of the F2 formulation at a dose
of 46 mg/kg body weight for seven weeks[19]. The outcomes revealed substantial therapeutic potential: mice
treated with F2 demonstrated a marked reduction in body weight gain compared to untreated controls. This
was accompanied by an improved food efficiency ratio, indicating a more favorable balance between caloric intake
and body weight. In addition, there was a significant reduction in white adipose tissue mass, a key indicator of
visceral fat accumulation. These physiological improvements were supported by biochemical analyses showing
lowered serum triglycerides and total cholesterol levels, suggesting effective lipid metabolism modulation.
Moreover, insulin sensitivity was notably enhanced, as F2 treatment attenuated the insulin resistance typically
induced by the high-fat diet, indicating a beneficial effect on glucose homeostasis[19].
At the molecular level, the F2 formulation exerted significant regulatory effects on adipogenic pathways within
epididymal fat tissue[19]. There was downregulation of critical adipogenic transcription factors such as
peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding protein 1c
(SREBP-1c), and adipocyte protein 2 (aP2), which collectively contribute to fat cell differentiation and lipid
storage. Histological analysis of liver tissues further demonstrated reduced hepatic steatosis, highlighting F2’s
role in mitigating fatty liver development associated with obesity[19]. The analytical rigor of the study was
ensured by employing validated ultra-performance liquid chromatography with diode-array detection (UPLC-
DAD) assays to quantify and standardize the presence of reference phytochemicals including astragalin, ellagic
acid, fisetin, fustin, and sulfuretin in the formulation[19]. This analytical control strengthens the reproducibility
and quality of the herbal blend. Overall, the study underscores the synergistic action of F2’s constituent
compounds in targeting multiple facets of obesity and metabolic dysfunction, suggesting its promise as a natural
therapeutic strategy for managing diet-induced obesity and associated metabolic derangements.
Other Polyherbal Combinations
A comprehensive review of the literature identified 25 animal studies investigating various polyherbal blends
targeting metabolic syndrome (MetS) components, such as obesity, hypertension, dyslipidemia, and insulin
resistance[20]. These studies primarily used rodent models that emulate human metabolic dysfunctions,
offering valuable preclinical insights[20]. Among the most notable combinations were blends containing
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Curcuma longa (turmeric), Salacia reticulata, Gymnema sylvestre, Emblica officinalis, and Terminalia chebula. These
blends consistently demonstrated significant improvements in multiple metabolic parameters, including
reductions in body weight, blood pressure, triglycerides, and fasting glucose levels, alongside increases in high-
density lipoprotein (HDL) cholesterol in rodents[21]. Similarly, another combination consisting of Glycyrrhiza
uralensis (licorice), Rheum undulatum, Prunus persica, and Cinnamomum cassia was reported to modulate all major
components of MetS effectively, suggesting broad-spectrum benefits in metabolic regulation[22]. Additionally,
traditional multi-herbal decoctions such as Lingguizhugan have shown potential synergistic effects, although
detailed dosing data and pharmacokinetic profiles were often lacking, limiting the ability to fully evaluate their Page | 84
therapeutic window and efficacy[23].
Other polyherbal blends like red ginseng combined with Polygonum multiflorum or Curcuma longa with Artemisia
iwayomogi also produced promising results, reinforcing the concept that herbal synergy can enhance therapeutic
outcomes in metabolic disorders[24]. However, a common limitation across most studies was the absence of
rigorous experimental design features, such as appropriate controls, randomized dosing, and clear dose-
dependency assessments[24]. Many studies relied on single-dose experiments or lacked placebo groups,
reducing the robustness of the conclusions. Moreover, standardization of herbal extracts and identification of
active constituents were often insufficient, which hinders reproducibility and translational potential[25]. These
shortcomings underscore the urgent need for improved experimental methodologies in polyherbal research,
including validated phytochemical standardization, dose-response studies, and long-term safety evaluations.
Addressing these gaps will enhance the scientific credibility of polyherbal formulations and facilitate their
development into evidence-based therapeutics for metabolic syndrome and related disorders.
Single Herb and Compound Models
Recent preclinical studies have highlighted the synergistic potential of specific herbal blends and isolated
phytochemicals in combating obesity and metabolic syndrome (MetS). For instance, formulations such as F2,
which consist of multi-herbal mixtures, have demonstrated pronounced synergistic effects in animal models and
in vitro systems. These blends often combine herbs with complementary actions, resulting in enhanced efficacy
compared to individual components[26]. In several studies, such herbal combinations significantly reduced
weight gain, adipocyte hypertrophy, and serum lipid levels in high-fat diet (HFD)-induced obese models[27].
These findings suggest that multi-compound herbal formulas may exert broad-spectrum metabolic regulatory
effects, making them promising candidates for integrative obesity therapy[27]. This approach mirrors
traditional medicinal systems where polyherbal prescriptions are frequently employed for complex disorders
like obesity, which involve multiple dysregulated pathways.
Beyond multi-herb formulas, individual phytochemicals and defined combinations also show considerable anti-
obesity potential. A notable example includes the co-administration of berberine, catechin, and capsaicin, which
collectively inhibited adipocyte differentiation in 3T3-L1 preadipocyte cells[28]. Each compound targets
different cellular pathways—berberine modulates AMPK activity, catechins exhibit antioxidant effects, and
capsaicin activates thermogenic pathways—highlighting their complementary mechanisms[29]. Moreover, a
study involving L-carnitine combined with a herbal mixture demonstrated significant physiological benefits in
HFD-fed rats[29–31]. This combination not only reduced body weight but also improved lipid profiles,
enhanced antioxidant enzyme activity, and lowered oxidative stress markers. Such findings underscore the
therapeutic promise of integrating nutraceuticals and bioactive plant compounds for managing metabolic
dysfunction. These models offer valuable insights into the pharmacodynamic interactions among bioactive
compounds, paving the way for future clinical applications that are both effective and safer than conventional
pharmacotherapy.
Mechanisms of Action
The therapeutic efficacy of many herbal and natural compounds in treating obesity and metabolic syndrome is
largely attributed to their diverse and complementary mechanisms of action[32]. One of the most commonly
observed effects is appetite suppression, which leads to a significant reduction in overall energy intake[32]. This
is often mediated through the modulation of central nervous system pathways involving neurotransmitters such
as serotonin and dopamine, or through peripheral signals like leptin and ghrelin. Additionally, these compounds
frequently enhance thermogenesis and elevate the basal metabolic rate by activating brown adipose tissue or
inducing the expression of uncoupling proteins, thereby increasing energy expenditure even in the absence of
physical activity[33]. These combined effects help create a negative energy balance that promotes fat loss over
time.
Furthermore, several natural agents exert anti-obesity actions through direct modulation of lipid metabolism.
Pancreatic lipase inhibition, for instance, reduces fat absorption in the gastrointestinal tract, thereby limiting
caloric uptake from dietary fats[34]. Some compounds also improve insulin sensitivity, which is particularly
beneficial for individuals with MetS. This is achieved through the regulation of adipokines like adiponectin and
the facilitation of glucose transporter type 4 (GLUT4) translocation, leading to enhanced glucose uptake and
reduced insulin resistance. Many of these herbs and phytochemicals also possess potent antioxidant and anti-
inflammatory properties, which are crucial for mitigating oxidative stress and chronic inflammation—both

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hallmarks of metabolic syndrome[34]. By neutralizing reactive oxygen species (ROS) and downregulating pro-
inflammatory cytokines such as TNF-α and IL-6, these compounds help restore metabolic homeostasis and
protect against obesity-related comorbidities. Collectively, these multifaceted actions make natural compounds
valuable tools in both the prevention and management of metabolic disorders[35].
Clinical Evidence in Humans
Meta-Analyses and Systematic Reviews
A comprehensive 2019 meta-analysis encompassing 279 randomized controlled trials (RCTs) investigated the
effectiveness of plant-derived products in managing obesity and metabolic syndrome (MetS)[36]. This large-
Page | 85
scale review highlighted a significant impact of various botanical agents on key metabolic indicators such as
body weight, body mass index (BMI), waist-to-hip circumference, and lipid profiles. Notably, several plants
including Camellia sinensis (green tea), Phaseolus vulgaris (white kidney bean), Garcinia cambogia, Nigella sativa
(black cumin), puerh tea, Irvingia gabonensis, and Caralluma fimbriata demonstrated statistically and clinically
meaningful reductions in body weight and metabolic risk markers[37]. The findings underscored the potential
of phytotherapeutic interventions as complementary strategies in the clinical management of obesity and its
associated complications.
Among these botanicals, P. vulgaris and N. sativa emerged as particularly efficacious. P. vulgaris, through its α-
amylase inhibitory properties, contributed significantly to reductions in body weight, likely by reducing
carbohydrate absorption and promoting satiety[38]. On the other hand, N. sativa showed strong lipid-
modulating effects, especially in lowering triglyceride levels, suggesting its potential for managing dyslipidemia
in MetS[38]. These outcomes offer promising directions for future clinical trials and pharmacological
development, but also highlight the need for caution due to the heterogeneity in trial quality and intervention
protocols. Systematic reviews such as this provide valuable aggregated evidence but call attention to critical
gaps in long-term safety data, dosage standardization, and the mechanisms underpinning observed effects.
Single-Herb Trials
Individual herb-based clinical trials have provided further insight into the potential efficacy of specific botanicals
in the management of obesity and metabolic risk factors. For example, green tea catechins, particularly
epigallocatechin gallate (EGCG), have shown consistent benefits in reducing body weight (standardized mean
difference [SMD] –0.75), BMI (–1.2), waist circumference (–1.71 cm), and total cholesterol levels (–0.43)[39].
These effects are likely attributable to enhanced fat oxidation, increased energy expenditure, and improved lipid
metabolism[40]. Similarly, Phaseolus vulgaris extracts have demonstrated moderate but significant
improvements in weight (SMD –0.88), mainly through inhibition of starch digestion and appetite
suppression[41]. Nigella sativa has shown strong triglyceride-lowering effects (SMD –1.67), possibly due to its
bioactive compound thymoquinone, which exerts antioxidant and anti-inflammatory properties[42].
Other botanicals like Irvingia gabonensis, Cissus quadrangularis, and Caralluma fimbriata have also shown
promising outcomes in smaller trials, particularly in supporting weight loss[43]. These herbs are believed to
act via diverse pathways including appetite suppression, modulation of adipogenesis, and improvement of insulin
sensitivity[43]. Additionally, Aloe vera gel supplementation has been linked to reductions in fat mass and
improvements in glycemic control and lipid profiles, especially in obese or prediabetic individuals. Ocimum
basilicum (basil leaf) has demonstrated hypoglycemic effects in patients with type 2 diabetes mellitus (T2DM),
reducing both fasting and postprandial glucose levels[44]. Despite these encouraging findings, the overall
evidence base is constrained by the limited scale and duration of these studies, necessitating more robust, long-
term trials to validate efficacy and determine safety across diverse populations.
Safety & Limitations
Despite their promising therapeutic profiles, plant-derived anti-obesity agents are not without limitations. Most
clinical trials conducted so far have been of relatively short duration, typically less than 12 weeks, and generally
report good tolerability with few adverse events. However, the long-term safety of these botanicals remains
largely unexamined[45]. Potential herb-drug interactions, especially in patients on multiple medications for
comorbid conditions such as diabetes, hypertension, or dyslipidemia, are insufficiently documented. This lack of
pharmacovigilance is a significant concern given the increasing use of herbal products as complementary or
alternative therapies[45].
Moreover, the methodological rigor of many studies in this field is variable. Issues such as small sample sizes,
lack of randomization, inadequate blinding, and inconsistent outcome reporting hinder the ability to draw
definitive conclusions[46]. Another major limitation lies in the absence of standardized extracts, making it
difficult to compare results across studies or replicate findings[46]. The quality and composition of herbal
supplements can vary widely depending on geographical origin, processing methods, and storage
conditions[46]. These limitations highlight the urgent need for more rigorous, large-scale randomized
controlled trials with standardized formulations and robust safety monitoring protocols. Only then can the true
potential and applicability of these botanicals in clinical practice be accurately assessed.
DISCUSSION

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Multi-Targeted Synergy
Herbal formulations composed of multiple botanicals have demonstrated promising efficacy in the management
of obesity-related metabolic disorders due to their ability to exert simultaneous effects on several biological
targets[47]. These natural mixtures often contain bioactive compounds that work in concert to modulate key
physiological processes such as adipogenesis, glucose homeostasis, inflammation, and oxidative stress[47]. The
synergistic or additive interactions between these compounds can enhance therapeutic efficacy beyond what is
achievable with single-ingredient interventions. This multi-targeted mechanism is particularly valuable in
complex diseases like obesity, where multiple pathways are dysregulated. For example, certain polyherbal Page | 86
formulations can inhibit adipocyte differentiation while also improving insulin sensitivity and reducing pro-
inflammatory cytokines, offering a holistic therapeutic benefit[48].
Standardization techniques, such as Ultra Performance Liquid Chromatography with Diode-Array Detection
(UPLC-DAD), have significantly advanced the reproducibility and quality control of herbal preparations[49].
These analytical tools allow for the consistent quantification of bioactive markers, ensuring batch-to-batch
uniformity, which is essential for clinical reliability and regulatory approval. A standardized formulation, such
as the referenced F2 compound evaluated in peer-reviewed studies, illustrates the potential of integrating
advanced analytical chemistry into herbal medicine development. As a result, combining traditional
ethnopharmacological knowledge with modern standardization techniques holds promise for optimizing the
therapeutic potential of multi-herbal regimens[49].
Challenges to Clinical Translation
Despite growing evidence supporting the efficacy of herbal formulations, several critical challenges hinder their
clinical translation. A primary concern is the lack of comprehensive standardization practices across
formulations[50]. Many herbal products on the market lack rigorous quality control measures, resulting in
inconsistencies in bioactive compound content and therapeutic potency. Quantifying bioactive markers and
establishing dose consistency is vital for translating preclinical success into reproducible clinical outcomes.
Moreover, randomized controlled trials (RCTs) exploring herbal interventions often suffer from small sample
sizes, poor methodological rigor, or short durations, making it difficult to draw definitive conclusions about
long-term safety and efficacy[51].
Safety remains another major hurdle. Herb–drug interactions, especially those involving cytochrome P450
enzymes, may alter the pharmacokinetics of co-administered drugs, leading to adverse effects or therapeutic
failure[52]. These interactions require thorough pharmacovigilance and mechanistic profiling. Furthermore,
regulatory ambiguities—such as whether a product is classified as a supplement or a drug can influence the
stringency of clinical trial design and approval pathways[52]. Without clear classification, navigating global
regulatory frameworks becomes complex. Finally, the mechanistic understanding of herbal therapies is still
evolving. Systems biology approaches, including genomics, proteomics, and metabolomics, combined with
advanced in vitro and in vivo models, can provide much-needed clarity on the molecular underpinnings of herbal
efficacy, paving the way for more informed clinical applications.
Future Directions
The future of herbal medicine in managing metabolic disorders lies in the integration of herbal blends with
conventional care and lifestyle interventions. This approach includes conducting well-designed integrative
clinical trials that evaluate herbal formulations alongside standard pharmacotherapies and personalized diet and
exercise programs. These studies should be powered to detect long-term clinical benefits and safety outcomes.
Additionally, pharmacokinetic investigations are essential to understand how herbal compounds are absorbed,
metabolized, and eliminated, as well as to establish dose-response relationships. This information will support
dose optimization and minimize toxicity, enhancing clinical reliability and regulatory acceptance.
Innovations in formulation technologies—such as nanoencapsulation and the use of bioenhancers—are also
promising avenues to improve the bioavailability and therapeutic efficacy of herbal compounds. Furthermore,
advances in precision medicine provide opportunities to tailor herbal interventions based on an individual’s
genetic background or metabolic profile, increasing the likelihood of treatment success. Personalized herbal
medicine, informed by omics data and systems biology, could revolutionize how these natural therapies are
prescribed. Lastly, synthesizing global evidence through meta-analyses and integrating ethnopharmacological
wisdom into clinical guidelines can support broader primary care adoption. This multidimensional strategy will
help bridge the gap between traditional practices and evidence-based medicine, enabling herbal therapies to play
a more prominent role in modern healthcare.
CONCLUSION
Traditional herbal formulations offer promising multi-target therapies for metabolic syndrome, with strong
preclinical data and emerging clinical support. Their complex activity profile—spanning adipogenesis
inhibition, lipase activity, insulin signaling, and inflammation—provides a compelling case for broader adoption.
However, realization of their full potential demands rigor: standardized preparation, robust clinical trials, safety
evaluation, mechanistic studies, and regulatory pathways. With these foundations, herbal formulations may
become valuable tools in combating the metabolic syndrome epidemic.

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CITE AS: Nyiramana Mukamurera P. (2025). The Role of Traditional

Herbal Formulations in Managing Metabolic Syndrome: Evidence from
Obesity and Diabetes Models. EURASIAN EXPERIMENT JOURNAL OF
MEDICINE AND MEDICAL SCIENCES, 6(3):82-89

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original work is properly cited