The Role of Medicinal Herbs in the Management of Metabolic Syndrome: A Comprehensive Review

Illnesses including cancer, diabetes, bone metabolic disease, fatty liver, obesity, cardiovascular disease, and others are referred to as metabolic illnesses or metabolic syndromes because they are linked to abnormalities in the metabolism of substances like glucose, fat, or protein(1). When three or more of the five criteria are satisfied, metabolic syndrome is diagnosed(2). The primary cause of metabolic syndrome is thought to be insulin resistance. Increased resistance will result in increased insulin secretion and metabolic syndrome. Insulin resistance is typically linked to genetic factors, autonomic hyperactivity, stress, obesity, and decreased physical exercise(3). The metabolic syndrome is a group of metabolic diseases caused by aging, ethnicity, stress, poor nutrition, genetic predisposition, and decreased physical activity. Despite the existence of conventional pharmaceutical treatments for metabolic syndrome, their limited use is ascribed to their high expense and side effects. In order to manage this illness, natural products with less adverse impacts have been studied(4). The purpose of this review of the literature is to investigate how natural products—such as vitamins, minerals, probiotics, botanicals, herbs, and dietary supplements—can help manage metabolic syndrome(5). Changes in a population's metabolic profile that are directly related to their daily routines are known as lifestyle illnesses. Unorganized eating habits, unoccupied exercise activities, etc.(6). are the main causes of lifestyle disorders. As obesity rates rise, metabolic syndrome—a prevalent metabolic condition—becomes worse. According to the WHO, metabolic syndrome, often referred to as syndrome X, insulin resistance, and other names, is a pathologic condition marked by hypertension, hyperlipidemia, abdominal obesity, and insulin resistance(7). Other comorbidities include nonalcoholic fatty liver disease, prothrombotic disorders, proinflammatory states, and reproductive abnormalities(4). Deficits in protein, glucose, lipids, and carbohydrates are among the metabolic diseases that make up the metabolic syndrome (MetS). Atherosclerotic cardiovascular diseases (ASCVD) and type 2 diabetes risk factors are combined to define it. These risk factors cause abnormal cholesterol or triglyceride levels, obesity, extra belly fat, high blood pressure, high blood sugar, or diabetes(8).  Due to its natural origin and fewer side effects, herbal medicines have become increasingly popular in both developed and developing nations, and their area has grown exponentially in the last several years. Numerous conventional medications are made from organic materials, minerals, and medicinal plants(9). The Indian traditional health care system uses herbal preparations that contain a few medicinal herbs known as rasayana, which have been utilized for more than a millennium. In the Indian medical system, the majority of practitioners create and administer their own medications(10). 21,000 plants are listed by the World Health Organization (WHO) as being utilized for medicinal purposes worldwide. 150 of these 2500 species are widely used commercially, with the majority occurring in India. . India is referred to as the world's botanical paradise and is the world's largest producer of medicinal herbs(11).

Figure 2. The Metabolic Syndrome

Types of metabolic syndrome

There are various types of metabolic syndrome Diabetes, Gaucher disease, Mitochondrial disease, Hypertension, Cholesterol gallstone, Elevated plasma glucose, Obesity, Phenylketonuria(12).

Diabetes

There are two types of diabetes

There are two types of diabetes

Type 1 & Type 2

Diabetes is a long-term metabolic disease that significantly affects sufferers' socioeconomic standing. In certain wealthy nations, The incidence of diabetes has gradually risen throughout the last few decades. Diseases Associated with Lifestyle and Metabolic Syndrome 2. According to research from the International Diabetes Federation (IDF), if effective treatment measures are not put in place, the number of people with diabetes might rise by 693 million by 2045(13). Figure 1 shows the prevalence and incidence of diabetes in Indian communities. Diabetes is becoming a bigger problem in India, according to IDF data. Patients with diabetes range in age from 20 to 70 years, with an estimated 8.7% of them having the disease(14). Formally speaking, diabetes mellitus is a metabolic disease that is associated with the metabolism of proteins, fats, and carbohydrates. Insulin resistance and/or insufficiency are the next symptoms. Weight loss, blurred vision, thirst, and polyuria are the hallmark signs and symptoms of diabetes mellitus. Studies from the past ten years indicate that between 25% and 33% of persons from different ethnic backgrounds fulfill the parameters for the metabolic syndrome. As people age, metabolic syndrome becomes more prevalent(15). It has been demonstrated that certain ethnic groups are more likely to have type 2 diabetes mellitus (T2DM); for example, only 4.30% of Chinese Americans and 15% of American Indians have T2DM. Abdominal obesity and metabolic syndrome are more common in South Asian Americans than in other ethnic groups(16).

Figure 1. Rate of diabetes patient in India in millions

The prevalence of type 2 diabetes mellitus (T2DM) is increasing, and it has progressively turned into an epidemic that affects public health worldwide(17). By 2045, 783 million adults are predicted to have diabetes, according to new data released by the International Diabetes Federation(18). It is typified by consistently elevated blood sugar levels brought on by insulin resistance or insufficiency. Nowadays, the standard treatment for type 2 diabetes is diet-based, with the addition of insulin injections or oral medications for individuals who are unable to control their blood glucose levels with diet alone(19). Type 1 diabetes mellitus (DM) and Type 2 diabetes mellitus (DM) are the two main forms of the disease. Because the pancreatic β cells have been completely destroyed, type 1 diabetes is characterized by a complete lack of insulin production. This can be acquired or epigenetic (autoimmune/mutation). Just 10% of all diabetes patients are T1DM. Although it affects people of all ages, children under five are most affected. T2DM, which makes up 90% of all DM cases, is defined by a persistent rise in blood glucose levels (chronic hyperglycemia) brought on by a malfunction in either the receptor for insulin (insulin resistance) or the production of insulin (impaired β cell activity)(20).  Gestational diabetes mellitus (GDM) is another mild form of diabetes mellitus that develops during pregnancy because of elevated blood glucose levels. Diabetes frequently manifests as polyuria (increased urination), polyphagia (increased appetite), polydipsia (increased thirst), and weight loss (caused by excessive protein oxidation and glycation)(21).

Obesity

Defend is condition of excessive fat storage, A major public health problem is obesity, affecting about 2 billion people globally(22). Increased healthcare expenses, reduced productivity, and unfavorable social and economic consequences are all caused by obesity. Furthermore, obesity is closely linked to metabolic syndrome, which includes type 2 diabetes, dyslipidemia, hypertension, and cardiovascular disease, according to numerous research. As a result, obesity poses a risk to public health and raises mortality and lowers quality of life. Headache, nausea, dry mouth, and sleeplessness(23). Unfortunately, obesity is still difficult to avoid and manage. Making the right dietary and lifestyle choices has been proposed as the most effective strategy to fight obesity, but long-term lifestyle adjustments are challenging(24). However, it has been noted that including functional foods in the diet can help prevent or treat obesity. Vascular tissues grow as a result of increased cytokine production brought on by the buildup of extra adipocytes. The repercussions of atherosclerosis, cardiovascular abnormalities, and hyperlipidemia are all interrelated. Because obesity increases the risk of several diseases, including colon cancer, gallstones, liver and gut disease, etc., atherosclerosis plays a role in obesity. The prevention and treatment of these co-morbidities can therefore be achieved through the management of obesity(25). Increasing calorie expenditure or decreasing appetite can aid with weight control. The hormones and receptors that control hunger and satiety also control appetite. Sitting less can also lessen the accumulation of white adipose tissue. Consequently, inhibition of adiponectin would be beneficial in preventing carcinogenesis linked to fat. The release of insulin is increased by hormones like cortisol, norepinephrine, and adrenaline(26). Insulin regulates blood glucose levels and body fat. Molecules 2022, 27, 1713 4 of 37? Consequently, any one component of this fundamental physiological cycle is out of balance, leading to obesity. Insulin is linked to diabetes and is crucial in the management of obesity. Dopamine helps the digestive tract and pancreas release their hormones and controls fat. Obesity can result from hormone imbalances, but homeostatic regulation governs the hormones that maintain hunger, satiety, and body fat. Thus, these components and their effects are severe when developing new anti-obesity medications(27).

Table 1. According to (WHO) Classification of weight.

 Hypertension

A chronic medical disease known as hypertension (HTN) or high blood pressure (BP) is characterized by excessive blood pressure in the arteries. It can be categorized as secondary or primary (essential)(28) . Primary hypertension, or high blood pressure for which no known medical reason can be identified, accounts for 90 to 95 percent of cases. The other 5–10% of instances, referred to as secondary hypertension, are brought on by other illnesses that impact the heart, arteries, kidneys, or endocrine system(29). HTN is a major cause of chronic kidney failure and a risk factor for heart attacks, strokes, heart failure, and arterial aneurysms. A moderate increase in arterial blood pressure reduces life expectancy. Medication, food, and lifestyle modifications can all help regulate blood pressure and lower the risk of related health issues(30).

Classification

In general, diastolic and systolic blood pressures are employed to classify hypertension. Heartbeat-related The term systolic blood pressure refers to blood pressure.  A heart's diastolic pressure is measured in between heartbeats. A person is categorized if their systolic or diastolic blood pressure values above the usual allowed norms for their age, they are classified as pre-HTN or HTN. HTN stage I, HTN stage II, and isolated systolic hypertension are some of the several subclassifications. of hypertensionsystolic or diastolic blood pressure readings that are greater above the commonly recognized normal levels for their age, as pre-HTN or HTN. Among the other subclassifications are isolated systolic hypertension, HTN stage I, and HTN stage II. People older than A person is considered to have hypertension if their blood pressure consistently remains at least 140 mmHg systolic or 90 mmHg diastolic. For those the diabetes or renal illness who also have blood pressure readings more than 130/80 mmHg, additional medication is required. Additionally, HTN is categorized as medication resistant. are unable to lower blood pressure to normal. Exercise hypertension is the term used to describe excessively elevated blood pressure during physical activity. Systolic measurements when exercising fall within the usual range of 200 to 230 mmHg. Exercise hypertension may be a sign that a person is susceptible to resting-state hypertension(31).

Table 2. Blood Pressure Ranges

Cholesterol

There are two types of cholesterol

• Low-density lipoprotein (LDL) cholesterol: People frequently refer to this type of cholesterol as "bad." When levels are high, LDL can contribute to blocked arteries.

• High-density lipoprotein (HDL) cholesterol: This type of cholesterol is sometimes referred to as "good." LDL cholesterol is reduced in the blood by HDL.

Figure 2. Types Of Cholesterol

Hyperinsulinemia or insulin resistance combined with dyslipidemia (high triglycerides, low HDL-C) level. Other phenotypes, including altered fibrinolysis, microalbuminuria, small dense low-density lipoprotein (LDL) particles, and indicators of acute phase reactants, have been linked to central obesity. It is not unexpected that the prevalence of multiple sclerosis (MS) and its effect on the chance  of coronary heart disease (CHD) in the community were not readily apparent given the rapidly changing understanding of risk factor clusters(32). Therefore, it is appropriate to assess the incidence of MS and its impact on the risk of CHD in both high and low LDL-cholesterol (LDL-C) populations [11]. The National Cholesterol Education Program's Third Adult Treatment Panel (NCEP ATPIII) regarded T2D as the pinnacle of MetS and MetS as a risk factor for CVD. This panel, which was primarily made up of lipidologists and cardiologists, created a straightforward clinical definition of the MetS that omitted the requirement to determine IR and included fasting hyperglycemia (without an upper limit) as one of its components(32).

Ayurveda
India is referred to as the world's Botanical Garden. There are numerous Indian medicines that are utilized to treat metabolic syndrome(33).
The Doshic dominance of the disease is the focus of the dietary and lifestyle management recommendations; patients with Kaphaja Prameha (Prameha in which Kapha is the predominant Dosha) should eat more catabolic food, while those with Vataja Prameha (Prameha in which Vata is the predominant Dosha) should eat more anabolic food.(34). For patients with Vataja Prameha, the Charaka Samhita and Sushruta Samhita both suggest anabolic therapies called Santarpana and Brimhana(35). Amalaki and Haridra (turmeric) are regarded in Ayurveda as one of the most effective straightforward herbal remedies for Prameha. They can be consumed as a part of the diet or in powdered form because Amalaki is a seasonal fruit, and Haridra is a spice that is frequently used in the cooking of many different foods. Other spices with antidiabetic qualities include cinnamon, Jeeraka (Cuminum cyminum Linn., cumin), Rasona (Allium sativum Linn., garlic), Shunthi (Zingiber offcinale Rosc., ginger), and Methika (Trigonella foenum-graecum Linn., fenugreek).(36). People with type 2 diabetes who consume cinnamon have lower levels of triglycerides, low-density lipoprotein (LDL), and serum glucose.33, Cumin lowers plasma cholesterol, triglycerides, glycosylated hemoglobin, and blood glucose in rats with diabetes caused by alloxan(37).

General Description

1. Cinnamon

One frequent herb that is used in both food and industry is cinnamon. Its oil may be used as an antiseptic, antitussive, antibacterial, antioxidant, or an analgesic in traditional medicine(38). Traditional medicine and new scientific research support the use of the active ingredients in cinnamon, such as cinnamon aldehyde. There are several therapeutic applications for eugenol, cinnamonate, and cinnamic acid aqueous and alcoholic extracts. Numerous symptoms of Metabolic Syndrome, including high blood pressure, dyslipidemia, obesity, and elevated blood glucose, can be alleviated by cinnamon extracts. Cinnamon has been demonstrated in studies to be a cardiovascular preventative agent and may help lessen the challenges associated with Metabolic Syndrome because of its anti-diabetic, antioxidant, anti-inflammatory, and lipid profile-beneficial qualities. Frequently called the "Ceylon cinnamon tree" or the "true cinnamon tree" Cinnamomum verum (previously C. zeylanicum) is a medicinal plant that is a member of the Lauraceae family. The little tropical tree C. verum is native to East and Middle Asia, including India and Sri Lanka(39).

Phamacognostical Characteristics

The leathery, typically opposite, lanceolate to ovate leaves of the C. verum tree, which reaches a height of about 10 m, are lanceolate to ovate and have sharp points. The tubular, six-lobed, pale-yellow flowers are borne in panicles as long as the leaves. When ripe, the little fruit, which is 1 to 1.5 cm long, becomes black(40).

2. Zingiber officinale

Many dishes and beverages employ ginger, or Zingiber officinale, as a flavoring. Since ancient times, people all over the world have utilized it as a natural cure to treat a variety of illnesses(41). According to phytochemical investigation, Zingiber officinale contains non-volatile substances such zingiberone, zingiberole, and zingiberene as well as phenolic compounds like gingerols, shogaols, and paradols. In addition to decreasing blood pressure and blood sugar, ginger has hypolipidemic, hypoglycemic, immunomodulatory, antioxidant, antiemetic, and anti-inflammatory properties. Ginger is a hypoglycemic food additive that has shown promise in treating type 2 diabetes in humans, according to numerous research conducted on both humans and animals. In order to maintain blood glucose homeostasis, ginger works by regulating insulin secretion and encouraging glucose clearances in peripheral tissues that are insulin responsive(42). The well-known spice ginger is made from the rhizome plant Zingiber officinale Rosco (Zingiberaceae) and has been used extensively in cooking. It has a variety of phytochemicals and physiologically active substances, including shogaols and gingerols. In addition to its many traditional medicinal use, ginger and its primary bioactive ingredients have been shown to reduce obesity in cell lines and rodent animal models(43). For instance, administering ginger extract helps stop obesity resulting from a diet heavy in fat. In this study, we examined how ginger affected energy metabolites that are involved in the TCA cycle and glycolysis, as well as how ginger administration affected the levels of several important genes and proteins(44). Lastly, we suggested the chemical mechanism behind the browning action caused by ginger. The current study may provide new light on ginger's ability to prevent obesity(45)

3. Aloe vera Gel

Participants in the trial were type-2 diabetics with a diagnosis of hyperlipidemia and/or hypercholesterolemia. The randomized double-blind placebo-controlled clinical trial involved participants aged 40–60 who were receiving oral hypoglycemic drugs (metformin and glyburide) rather than anti-hyperlipidemic drugs [46]. In order to assess the antihyperlipidemic potential and safety factors, the test group (n = 33) received 300 mg of aloe vera capsules every 12 hours for two months. As a placebo, toast powder was provided to the other group. At the conclusion of the study period, the aloe vera therapy significantly reduced fasting blood glucose, HbA1c, total cholesterol, and LDL levels in comparison to the placebo. Throughout the course of the study, no negative effects of the therapy were noted. The leaf gel is suggested by the authors as an antihyperglycemic and antihyperlipidemic treatment for diabetic patients(46).

4.  Ashwagandha. (W. Somnifera)

Ashwagandha, or W. somnifera, is a member of the Solanaceae family. W. somnifera is categorized as a "Rasayana" in Ayurveda because of its anti-aging and health-promoting qualities. In many parts of the world, this significant medicinal herb is also utilized to treat a variety of illnesses(47). With its unique horse-like scent, the root has anti-microbial, anti-inflammatory, neuroprotective, antioxidant, and aphrodisiac qualities. Due to its reputation for promoting lifespan and rejuvenation, ashwagandha is widely used in both traditional and alternative medicine. The most well-known form of ashwagandha is fresh ashwagandha, or Nagori ashwagandha, and its roots and leaves are primarily utilized for a variety of therapeutic applications. The impact of several W. somnifera components and active substances on the risk variables linked to MetS is examined in this review(48). In Ayurveda, traditional plants like W. somnifera (ashwagandha) have long been used for therapeutic purposes. Recent research has shown that ashwagandha has a variety of possible medicinal benefits, particularly when it comes to its active ingredients, withanolides A and D. Through a number of mechanisms, including blocking HMG-CoA, increasing glucose absorption, and boosting insulin sensitivity, these substances show promise in preventing MetS(49).

5. Carica Papaya

The popular papaya, Carica papaya, is one of the plants having health benefits. This fruit has high levels contains bioactive substances, vitamins, and lipids are  prevent hypercholesterolemia, protect in opposition to oxidative stress and thrombogenesis, both lower inflammatory markers or anti-platelet aggregation—all of which can be brought on by obesity(50). Around the world, carica papaya is consumed unprocessed or transformed into pulp, jam, and confections. Other plant components, including as the The addition of leaves and seeds to various goods, such as flours and teas, to increase their nutritional content. Apart from minerals like potassium and magnesium and vitamin B complex like folate and Three important vitamin sources with potential antioxidant activity are present in the pulp composition, including pantothenic acid. A, C, and E. Food fibers are also present(51). Excessive body fat accumulation is the hallmark of obesity, which incorporates a number of ethological elements, including genetic, metabolic, social, behavioral, environmental, cultural, and psychological ones. Obesity can pose a major health risk. Excessive visceral fat accumulation is known to play a significant role in the emergence of metabolic disorders, such as arterial hypertension, dyslipidemia, and insulin resistance, as well as changes that support the onset of type 2 diabetes and cardiovascular diseases. Therefore, the collection of these risk factors, or a group of metabolic diseases linked to obesity, such as insulin resistance, atherogenic dyslipidemia, and hypertension, which might result in cardiovascular diseases, can be referred to as the metabolic syndrome(50).

6. Elettaria cardamomum (Cardamom)

Elettaria cardamomum, commonly referred to as cardamon, is a member of the Zingiberaceae family. It can be found in Bangladesh, Pakistan, Burma, the Indian subcontinent, and tropical and subtropical Asia. In numerous studies, cardamom and its active components have been shown to alter blood total cholesterol (TC), TG, LDL, and HDL. A thin, papery black shell envelops the triangular pod in cross-section of the tiny cardamom seeds(52).

7. Azadirachta indica (Neem)

An evergreen tree native to Southeast Asia, neem (Azadirachta indica) is found throughout the Indian subcontinent. The maximum height that this tree may reach is 15 to 20 meters, and occasionally up to 35 to 40 meters. The Persian language is the source of the word "A. indica." The dirakht means "tree," the Azad means "free," and "I" stands for "Indian origin(53)." The common names for neem include Nimbay, Veppai, Ariyaveppu, and Vepa in India. Blood pressure, hypertension, hypotension, antihypertensive, dyslipidemia, hyperlipidemia, high triglycerides, high cholesterol, and hypercholesterolemia Hyperglycemia, insulin, hypoglycemia ,antihyperglycemic, antidiabetic, blood glucose, neem, atherogenic, atherosclerosis, excessive weight, hunger, anti-obesity, diabetes, weight reduction, hypertriglyceridemia, and neem are all utilized as herbs(54).

8. Camellia sinensis. (Green tea)

Even though Camellia sinensis belongs to the family Theaceae., won't cause you to lose weight quickly, its leaves will increase your metabolic rate by 4% not including raising your heart rate since they promote fat oxidation or thermogenesis. According to a human study on green tea extract, males Those who consumed the epigallocatechin-3-gallate (EGCG) extract burnt more calories. each day than those in the placebo group. This suggests that the extract thermogenic properties could be crucial in reducing obesity(55).

9.Berberine

An alkaloid that is now attracting a lot of attention is berberine, which has potent pharmacological properties(56). Though it has long been utilized as a plant extract in traditional medicine, recent research techniques have shown that berberine is a promising treatment for modern illnesses(57). Recent research has validated the importance of its anticancer properties and its efficacy in treating cardiovascular, metabolic, or neurological conditions(58). The substance has undergone numerous clinical assessments in individuals with metabolic syndrome(56).

Figure 3. Used of berberine

Risk Factors of Metabolic Syndrome

Following factor that are chances to increase metabolic disease.

1. Age

Less than 10% of people in their 20s and 40% of adults in their 60s have MetS, a condition whose risk rises with age. Nonetheless, some studies indicate that roughly one out of every eight school-age children have three or more MetS components. Decades later, another study found a link between childhood MetS and adult cardiovascular disease (59).

2. Race

Less than 10% of persons in their 20s and 40% of adults in their 60s have MetS, a condition whose risk rises with age. Nonetheless, some studies indicate that roughly one out of every eight school-age children have three or more MetS components (60).

3. Obesity

The risk of MetS is increased if one's body mass index (BMI), which is a measurement of the proportion of body fat based on height and weight, is more than 25. Compared to excess fat on other body areas, such the hips, excess fat in the abdomen is a higher risk factor for heart disease. Consequently, abdominal obesity—that is, having an apple-shaped body rather than a pear-shaped one—also occurs(61).

4. History of Diabetes

The presence of a family history of type 2 diabetes or gestational diabetes during pregnancy increases the risk of developing Mets (62).

5. Other Disease

The risk of MetS is further increased by a diagnosis of polycystic ovarian syndrome, cardiovascular illness, gallstones, fatty liver, or breathing issues during sleep. These metabolic disorders impact a woman's hormones and reproductive system (38).

Figure 4. Risk Factor of Metabolic Syndromes

Lifestyle Caused Metabolic Syndrome

1. Diet

Among the most effective therapies to make everything better MetS problems is weight loss.  An imbalance in energy intake and expenditure is the main cause of overweight and obesity, which are parts of the metabolic syndrome. About 60% of people in India suffer from an unhealthy diet, which accounts for 20% of all fatalities in the nation. One way to manage MetS is to make the following dietary adjustments.(63).                                                                                                                                 

1. Lack of physical exercise

Despite the well-established and empirically validated health advantages of physical activity, about 70% of Polish males and more than 60% of Indian women do not routinely engage in physical activity(64). reducing triglyceride levels, raising HDL-C levels, and enhancing glycaemic control because of enhance tissue sensitivity to insulin, and lowering blood pressure are all significant advantages of physical activity as seen by the MetS [66]. According to the most recent guidelines from the European Society of Cardiology, an adult's weekly physical activity should be at least as high as possible to lower all-cause mortality, CV mortality, and morbidity.

2. Alcohol consumption

India's average annual alcohol intake is 10.6 liters per person. Numerous population studies demonstrate that "none is the lowest degree of alcohol safety." and drinking alcohol raises the risk of cardiovascular disease, overweight, obesity, depression, and suicide in addition to cancer. Alcohol's high calorie content and lack of nutrients cause it to have a negative impact on body weight. When it comes to MetS, alcohol also raises levels of uric acid, cholesterol, and blood pressure (65).

3. Sleep and Circadian Rhythm

Getting enough sleep, both in terms of quantity and quality, is essential to sustaining an ideal body weight. A person should aim for six to eight hours of sleep per night, or 1/3 to 1/4 of a day since there is a chance that this will result in weight gain. and various symptoms of Mets. with consistent wake-up or sleep schedules exposure to blue light from electronic devices that emit light, such as tablets and smartphones, Use the bed just for sleeping and having sex, and make the bedroom as dark as you can.(66) .