Multifaceted roles of herbal compounds in dyslipidemia management: Mechanistic and therapeutic perspectives of herbal medicine

 Corresponding author: Kante Manjusha Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution License 4.0. Multifaceted roles of herbal compounds in dyslipidemia management: Mechanistic and therapeutic perspectives of herbal medicine Kante Manjusha *, K. Jhansy Sree,Macha Indhu, Kausar Fatima, V. Padmaja and M. Sumakanth. Department of Pharmaceutical Chemistry, RBVRR Women’s College of Pharmacy, Hyderabad, Telangana, India. World Journal of Biology Pharmacy and Health Sciences, 2025, 22(02), 070-090 Publication history: Received on 18 March 2025; revised on 29 April 2025; accepted on 01 May 2025 Article DOI: https://doi.org/10.30574/wjbphs.2025.22.2.0456 Abstract Dyslipidemia, marked by abnormal lipid levels in the blood, is a significant risk factor for cardiovascular diseases. Although conventional treatments, including statins, bile acid sequestrants, and fibric acid derivatives, are widely prescribed, they are often associated with side effects, long-term use concerns and limited efficacy in certain individuals. This has spurred growing interest in alternative treatments, particularly herbal medicine to manage dyslipidemia. This project investigates the potential of various phytochemicals in regulating lipid profiles via several mechanisms such as inhibiting cholesterol absorption in enterocytes, Reducing cholesterol synthesis, Enhancing reverse cholesterol transport, Regulating hepatic lipid uptake, and Promoting cholesterol excretion in the liver. Additionally, many phytochemicals in herbal medicine exhibit other pharmacological properties including antioxidant, anti-inflammatory and cardioprotective effects. These complementary actions improve the overall management of dyslipidemia and contribute to reducing the risk of cardiovascular diseases. Keywords: Dyslipidemia; Herbal Medicine; Phytochemicals; Anti Hyperlipidemics; Pharmacological Actions 1. Introduction Lipids such as cholesterol and triglycerides are absorbed in the intestines and transported throughout the body by lipoproteins. They play vital roles in providing energy, producing steroid hormones and forming bile acids. Key elements involved in these processes include total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides which are shown in Figure1. An imbalance in any of these lipid components can lead to dyslipidemia—a condition marked by abnormal lipid levels in the blood, which increases the risk of cardiovascular diseases.1 World Journal of Biology Pharmacy and Health Sciences, 2025, 22(02), 070-090 71 Figure 1 Lipoprotien classification Dyslipidemia is classified into 2 types • Primary Dyslipidemia: it is also called familial due to genetic defects; it may be monogenic (single gene defect) or polygenic (multiple gene defects). Primary hyperlipidemia can usually be resolved into one of the abnormal lipoprotein patterns based on their deficiency. • Secondary Dyslipidemia: it is acquired and caused by lifestyle factors or other medical conditions that alter lipid levels. 1.1. Symptoms Generally, hyperlipidemia does not have any obvious symptoms but they are usually discovered during routine examination or until it reaches the danger stage of a stroke or heart attack. Patients with high blood cholesterol level or patients with the familial forms of the disorder can develop xanthomas which are deposits of cholesterol may form under the skin, especially under the eyes. At the same time, patients with elevated levels of triglycerides may develop numerous pimple-like lesions at different sites in their body shown in Figure2 and 3 2 Figure 2 Lesions World Journal of Biology Pharmacy and Health Sciences, 2025, 22(02), 070-090 72 Figure 3 Xanthomas 1.2. Mechanism of Dyslipidemia Figure 4 Mechanism of dyslipidemia World Journal of Biology Pharmacy and Health Sciences, 2025, 22(02), 070-090 73 1.3. Factors causing Dyslipidemia: Figure 5 Factors causing dyslipidemia 1.4. Complications of Dyslipidemia Hyperlipidemia can lead to a variety of complications, including atherosclerosis, fatty liver,cardiovascular and cerebrovascular diseases and impaired vision . Hyperlipidemia can also increase the risk of high blood pressure, pancreatitis, hepatitis, and Alzheimer's disease . It is recognized as a significant risk factor for the development of coronary heart disease and is strongly linked to conditions such as diabetes, insulin resistance, and obesity. Figure 6 Complications World Journal of Biology Pharmacy and Health Sciences, 2025, 22(02), 070-090 74 1.5. Anti Hyperlipidemic Agents2 Statins, Bile acid sequestrants, Fibric acid derivatives, Nicotinic acid derivatives, cholesterol absorption inhibitors are the mostly used anti hyperlipidaemic agents. But on long term use these drugs produce various side effects like Myalgia, Arrythmia, Gall stones, Myopathy and various GI disorders. 1.6. Introduction to herbal medicine • Herbal medicine is a type of medicine that uses plant parts to treat diseases, prevent illness and improve health. • Herbal medicine can serve as an alternative to conventional medicine owing to its low toxicity and beneficial effects. • Herbal medicine has the potential to enhance therapeutic effects with fewer side effects.3 1.7. Herbal Medicine in Management of Dyslipidemia • As many plants derived products have Anti-oxidant activity, they are very much helpful in management of Dyslipidemia. • Phytochemicals with antioxidant and anti-inflammatory properties have been used to protect the vascular endothelium, prevent lipid oxidation, and lower lipid levels. • The diversity and complexity of multicomponent Herbal Medicine enable the targeting of alternative pathways and biological processes to treat complex diseases such as dyslipidemia which is a consequence of multiple factors.therefore, its clinical manifestations are also complicated not only in terms of elevated serum lipid levels but also multifarious disorder .4 • A single phytochemical exhibits multiple mechanisms in management of Dyslipidemia • eg: Curcumin,Berberine{Inhibition of cholesterol absorption,suppression of cholesterol synthesis,hepatic lipid uptake regulation}, Naringin {Inhibition of cholesterol absorption,Promotion of reverse cholesterol synthesis},Puerarin{Inhibition of cholesterol absorption,Acceleration of cholesterol excretion in liver} 1.8. Mechanisms of Herbal Medicine in management of Dyslipidemia Many varieties of phytochemicals are used in Management of Dyslipidemia. Five lipid-lowering mechanisms of herbal medicines are: • Inhibition of cholesterol absorption in enterocytes • Reduction of cholesterol synthesis • Elevation of reverse cholesterol transport • Regulation of Hepatic lipid uptake • Promotion of cholesterol excretion in the liver. 2. Literature review 2.1. Inhibition of cholesterol absorption in enterocytes Herbal medicine inhibits cholesterol absorption. Dietary components and bile enter intestinal cells through the transmembrane protein Niemann-Pick C1-like 1 (NPC1L1), which transports them from the intestinal lumen to the brush border membrane of enterocytes. After entering enterocytes, freecholesterol (FC) is esterified to cholesterol esters (CEs) by acyl CoA: cholesterol acyl transferase (ACAT)-2 in the endoplasmic reticulum (ER). Cholesterol esters (CEs) and triglycerides (TGs) are then combined to form chylomicrons with the help of microsomal triglyceride transfer protein (MTTP), which are subsequently secreted into the lymphatic system.phytochemicals from herbal medicines could regulate these processes. • Inhibition of NPC1L1 substantially decreases intestinal cholesterol absorption, which is modulated by sterol regulatory element binding protein-2 (SREBP)-2 exhibited by curcumin, lycopene. • Berberine is responsible for the cholesterol-lowering effect by inhibiting intestinal ACAT activity. • Naringin, hesperetin inhibits the MTTP (microsomal steroid regulatory protien ). • Inhibition of MTTP leads to decreased apolipoprotein B (APOB) secretion and chylomicron assemblage by puerarin. • Camphene upregulates the expression of SREBP-1 and blocks MTTP activity. The MOA is explained in Figure75 World Journal of Biology Pharmacy and Health Sciences, 2025, 22(02), 070-090 75 Figure 7 Mechanism of Inhibition of cholsterol absorption 2.1.1. Curcumin It is a polyphenol obtained from rhizomes of Curcuma longa belonging to the family Zingiberaceae.The dosage is 200mg/day for 2weeks.Experimental studies were performed on Cancer coli cell lines and HFD (high fat diet) fed miceand it exhibits various pharmacological actions like Anti-inflammatory, Antioxidant, Antibacterial, Antifungal and anti-diabetic [5]6][7] Figure 8 curcumin structure Figure 9 Turmeric powder 2.1.2. Berberine It is an alkaloid obtained from roots of Coptis chinesis belonging to the family Berberidaceae. The dosage is 300-400mg. Experimental studies were performed on male sprague-Dawley rats on atherogenic diet and it exhibits various pharmacological actions like Anti-inflammatory, anti-cancer.[5][8] World Journal of Biology Pharmacy and Health Sciences, 2025, 22(02), 070-090 76 Figure 10 Berberine structure Figure 11 coptis chinensis 2.1.3. Camphene It is a monoterpene obtained from bark of chiosmastic gum oil which is a resinous secretion of Pistacia lentiscus belonging to the family Anacardiaceae . The dosage is 300 mg Experimental studies were performed on HepG2cells. It exhibits various pharmacological actions like Anti-inflammatory [5][9] Figure 12 Camphene structure Figure 13 pistacia lentiscus 2.1.4. Hesperetin and Naringin These are flavonoids obtained from citrus fruit, specifically from the peel of orange, grapefruits, lemons, and mandarins belonging to the family Rutaceae, Vitaceae. The dosage is 300mg per day. Experimental studies were performed on HepG2 cells (human hepatoma cells line) and it exhibits various pharmacological actions like Lowering blood sugar levels, reducing Lipid levels, anti-inflammatory activity.[5][10] World Journal of Biology Pharmacy and Health Sciences, 2025, 22(02), 070-090 77 Figure 14 Hesperetin structure Figure 15 Hesperetin containing fruits Figure 16 Naringin structure 2.1.5. Lycopene: Lycopene is a carotenoid obtained from fruits of Solanum lycopersium belonging to the family Solanaceae.The dosage is 15-45 mg per day. Experimental studies were performed on caco-2 cells. It exhibits various pharmacological actions like antioxidant activity [5][11] World Journal of Biology Pharmacy and Health Sciences, 2025, 22(02), 070-090 78 Figure 17 lycopene structure Figure 18 lycopene containing fruits 2.1.6. Psyllium Psyllium obtained from soluble fibers Plantago ovata belonging to the family Plantaginaceae. The dosage is 19-50 g per day.Experimental studies were performed on HFD fed mice.it exhibits various pharmacological actions like treats constipation [5] Figure 19 Psyllium structure Figure 20 Psyllium husk 2.2. Suppression of cholesterol synthesis Cholesterol synthesis is strictly regulated by a negative feedback mechanism. Low cholesterol can be achieved by inhibiting the biosynthesis of cholesterol. • Inhibition of HMGCOA activity by geraniol,Leoligin,curcumin,puerarin. • Promotion of the expression of AMPK by allicin, and curcumin. • Emodin could reduce the SCAP/SREBP pathway. World Journal of Biology Pharmacy and Health Sciences, 2025, 22(02), 070-090 85 2.4. Regulation Of Hepatic Lipid Uptake Hepatic lipid levels are governed by the balance between lipid acquisition and disposal constituting the four major pathways of hepatic lipid homeostasis which are, circulating lipid intake, de novo lipogenesis (DNL), fatty acid oxidation (FAO), and export of lipids as very-low-density lipoproteins (VLDLs) explained in fig 47 Figure 47 Mechanism of Hepatic lipid uptake Regulation The liver is the major site for cholesterol metabolism, where it takes up HDL-CE and LDL particles by scavenger receptor class B type I (SRBI) and the low-density lipoprotein receptor (LDLR), respectively. LDLR, a transmembrane glycoprotein, binds to LDL on the cell surface. Proprotein convertase subtilisin/kexin type 9 (PCSK9) posttranscriptionally downregulates the LDLR by binding to the receptor's epidermal growth factor repeat A on the cell surface and shuttling the LDLR to the lysosomes for degradation. Berberine, Tanshinone IIa and curcumin act by • Decreasing the serum levels of TG, TC, LDL-C levels and increasing serum HDL-C levels by Increasing the expression of PCSK9 via SREBP-2 activation • Lipid lowering effect by regulation of hepatic LDLR and PCSK9 expression to reduce lipid levels via the ERK signaling pathway 2.4.1. Tanshinone IIA It is a diterpene quinone compound is obtained from Dried roots of Salvia miltiorrhiza Bunge obtained from family Lamiaceae. The Dosage is 20mg/day.Experimental studies were performed on HepG2 cells and it exhibits various pharmacological actions like Anti-inflammatory, anti-oxidant, anti tumor, cardiovascular effects. [5][27] Figure 48 Tanshinone IIa structure Figure 49 Roots and plant of salvia miltiorrhiza World Journal of Biology Pharmacy and Health Sciences, 2025, 22(02), 070-090 86 2.5. Acceleration of cholesterol excretion in the liver: • Cholesterol transported into the liver and endogenously synthesised is lost from the body via biliary secretion after conversion to bile acids. • Microsomal cytochrome P450 cholesterol 7 alpha hydroxylase (CYP7A1) is the first rate-limiting enzyme in the neutral pathway of bile acid synthesis, which plays a vital role in the maintenance of cholesterol homeostasis explained in figure 50 Figure 50 Mechanism of accelaration of cholesterol excretion • Lipid‐lowering effect by Stimulation of CYP7A1 at mRNA level by Epicatechin and palmatine • Up-regulation of LDLR and CYP7A1 mRNA and protein expression by puerarin and palmatine • Activation of the PPARγ-ABCA1/CYP7A1 signaling pathway by Punicalagin and pomegranate ellagic acid. 2.5.1. Palmatine It is a alkaloid obtained from Roots of Coptis chinensis belonging to the family Berberdaceae . The Dosage is 100mg/kg every 2 weeks.Experimental studies were performed on HFD-fed hamsters and it exhibits various pharmacological actions like Anti-inflammatory,anti-bacterial, anti-oxidation and antiviral. [5][30] Figure 51 Palmatine structure Figure 52 Coptis chinensis roots World Journal of Biology Pharmacy and Health Sciences, 2025, 22(02), 070-090 87 2.5.2. Punicalagin It is a polyphenol compound is obtained from Fruits of Punica granatum belonging to the family Punicaceae. The Dosage is 60mg for 23 days .Experimental studies were performed on Steatotic L-02 hepatocytes and it exhibits various pharmacological actions like Anti-cancer, anti-inflammatory and anti-oxidant.[5][31] Figure 53 Punicalagin structure Figure 54 Pomogranate 2.6. Marketed herbal formulations used in management of Dyslipidemia Figure 55 Himalaya abana tablets Figure 56 Aimil Trimalip tablets World Journal of Biology Pharmacy and Health Sciences, 2025, 22(02), 070-090 88 Figure 57 Krishna’s cholesterol care juice Figure 58 Allen cholesterol drops 3. Conclusion A single phytochemical exhibits multiple mechanisms in management of Dyslipidemia i.e Curcumin, Berberine by Inhibition of cholesterol absorption, suppression of cholesterol synthesis and hepatic lipid uptake regulation, Naringin by Inhibition of cholesterol absorption and Promotion of reverse cholesterol synthesis, Puerarin by Inhibition of cholesterol absorption and acceleration of cholesterol excretion in liver. Most phytochemicals exhibit different pharmacological actions other than Anti hyperlipidemic activity like Anti ointment-inflammatory, cardio protective actions which helps in enhanced treatment of Dyslipidemia and also reduces the risk of cardiovascular diseases. Herbal formulations are able to regulate the transcription factors like LXR, SREBP, PPARα, and PPARγ which are involved in expression of Key molecules like NPC1L1, HMGCR, PCSK9 and CYP7A1 which plays a important role in lipid metabolism. The active components are diverse and include alkaloids (berberine), saponins (ginsenoside), polyphenols (pomegranate) and flavonoids (quercetin). Herbal medicines provide a promising and multifaceted approach to World Journal of Biology Pharmacy and Health Sciences, 2025, 22(02), 070-090 89 dyslipidaemia management, with the potential for complementary benefits beyond lipid regulation, contributing to overall cardiovascular health. Compliance with ethical standards Acknowledgements We thank the Principal and Management of RBVRR Women’s College of Pharmacy for the technical support. Disclosure of conflicts of interest The authors have no conflicts of interest to declare. References [1] Pappan N, Awosika AO, Rehman A. Dyslipidemia. 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