Phytochemical Analysis and Assessment of the Antihyperlipidemic, Antihypertensive, Antidiabetic, and Anti-Inflammatory Activities of Johrenia aromatica in HFD-Induced Hyperlipidemic Male Albino Rats: Biochemical and Histopathological Evidence
Keywords:
Johrenia aromatica, Dyslipidemia, traditional medicine, Phytochemicals, HFD-induced hyperlipidemiaAbstract
Background: Hyperlipidemia is one of the most modifiable risk factors for cardiovascular disease and is often linked to obesity, hypertension, chronic inflammation, and metabolic dysfunction. While traditional lipid-lowering medications have proven effective, the incorporation of plant-based therapeutics with a favorable safety profile continues to rise.
Aim: The present study aimed to explore the phytochemical composition and pharmacologic effects of the hydroalcoholic extract of Johrenia aromatica (J. aromatica) in high-fat diet (HFD)-induced hyperlipidemic rats.
Methods: Gas chromatography–Mass Spectrometry (GC–MS) was used to characterize the extract of J. aromatica. Thirty male rats were randomly divided into 5 groups: the normal control group, HFD plus atorvastatin (10 mg/kg), HFD plus JA (400 mg/kg), HFD plus JA (600 mg/kg), and HFDG groups. Biomarkers of body weight, blood pressure, lipids, liver and renal function, blood glucose, C-reactive protein, and liver and kidney histopathology were assessed. Results: Sixteen phytochemical constituents were identified. J. aromatica treatment resulted in significantly lower serum total cholesterol, triglycerides, low-density lipoprotein, and very-low-density lipoprotein, together with lower body weight and serum C-reactive protein, than in the untreated HFD rats. The 600 mg/kg dose additionally lowered blood glucose. No treatment-related hepatic or renal injury was detected by the biochemical markers and histopathological examination performed.
Conclusion: J. aromatica had anti-hyperlipidemic and anti-inflammatory effects while preserving hepatic and renal safety in HFD-induced hyperlipidemic rats. These preliminary findings identify the extract as a candidate for further preclinical investigation in dyslipidemia and related metabolic disorders; its mechanism of action requires clarification before any clinical application can be considered.
References
1. Afolayan, f. I. D., odeyemi, r. A. & salaam, r. A. 2024. In silico and in vivo evaluations of multistage antiplasmodial potency and toxicity profiling of n-hexadecanoic acid derived from vernonia amygdalina. Front pharmacol, 15, 1445905.
2. Ahmed, f. N., jaff, s. & mohammed, g. A. 2025a. Anti-hyperlipidemic effect of statins and the role of nanomedicine in enhancing their bioactivity: a narrative review. Journal of sulaimani medical college, 15, 1-11.
3. Ahmed, f. N., mohammed, h. H., mohammed, g. A. & rahim, m.-o. M. 2025b. Hyperlipidemia and its systemic effects: molecular mechanisms, clinical consequences, and therapeutic approaches: a narrative review. Journal of sulaimani medical college, 15, 71-88.
4. Ahmed, s. F. & ahmed, f. N. 2025. Antibacterial activity of celery (apium graveolens) extract against urinary tract infections. Al-mustansiriyah journal for pharmaceutical sciences, 25. Amin, k. A., sana'a, r. G., wala'a, g. H. & shima'a, m. R. 2014. Effects of orlistat and herbal mixture extract on renal function and oxidative stress biomarkers in a rat model of high fat diet. International journal of biochemistry research & review, 4, 173.
5. Aminuddin, a., lazim, m. R. M., hamid, a. A., hui, c. K., mohd yunus, m. H., kumar, j. & ugusman, a. 2020. The association between inflammation and pulse wave velocity in dyslipidemia: an evidence-based review. Mediators of inflammation, 2020.
6. Aparna, v., dileep, k. V., mandal, p. K., karthe, p., sadasivan, c. & haridas, m. 2012. Anti-inflammatory property of n-hexadecanoic acid: structural evidence and kinetic assessment. Chem biol drug des, 80, 434-9.
7. Ashraf, j., khan, m. A., minhaj, s., khatti, s., aarij, k. M., shehzad, m., khan, t. M. & khan, m. A. 2020. Statins and abnormal liver function tests: is there a correlation? Cureus, 12.
8. Ayoade, o. G., umoh, i. & amadi, c. 2020. Dyslipidemia and associated risk factors among nigerians with hypertension. Dubai medical journal, 3, 155-161.
9. Ballena-caicedo, j., zuzunaga-montoya, f. E., loayza-castro, j. A., vásquez-romero, l. E. M., tapia-limonchi, r., de carrillo, c. I. G. & vera-ponce, v. J. 2025. Global prevalence of dyslipidemias in the general adult population: a systematic review and meta-analysis. J health popul nutr, 44, 308.
10. Bharathi, r., prasanna, k., krishna, b. D., kariyil, b., krithiga, k. & dinesh, c. 2025. Study on the extraction yield of hydroethanolic extracts of medicinal plants using the cold maceration method. International journal of research in agronomy, 8, 156-162.
11. Brahmi, n., feriani, a., ben ali, m., hedfi, a., elleuch, a., ismail, i., albogami, b., saif, t., talarmin, h. & el feki, a. 2021. Potential hepatoprotective effect of cheatomorpha gracilis extract against high fat diet (hfd)-induced liver damage, and its characterization by hplc. Brazilian journal of biology, 82.
12. Carvalho, a., heimfarth, l., pereira, e., oliveira, f., de menezes, i. R., coutinho, h., picot, l., antoniolli, a., quintans, j. & quintans-júnior, l. 2020. Phytol, a chlorophyll component, produces antihyperalgesic, anti-inflammatory, and antiarthritic effects: possible nfκb pathway involvement and reduced levels of the proinflammatory cytokines tnf-α and il- 6. Journal of natural products, 83.
13. Chang, y. B., ahn, y., seo, d., bae, s., suh, h. J., hong, y. H. & jung, e. Y. 2023. Centella asiatica lowers body fat accumulation via regulating cholesterol homeostasis- and lipid metabolism-related genes in mice with high-fat, high-sugar diet-induced obesity. Applied biological chemistry, 66, 88.
14. Daugherty, a., rateri, d., hong, l. & balakrishnan, a. 2009. Measuring blood pressure in mice using volume pressure recording, a tail-cuff method. J vis exp.
15. Durrington, p., bashir, b. & soran, h. 2026. Hyperlipidemia. Metabolism of human diseases: organ physiology and pathophysiology. Springer.
16. Gebreegziabiher, g., belachew, t., mehari, k. & tamiru, d. 2021. Prevalence of dyslipidemia and associated risk factors among adult residents of mekelle city, northern ethiopia. Plos one, 16, e0243103.
17. Ghfil, z., aboalhur, f. J., mshachal, m. A. & alobaidi, a. A. A. 2025. Antioxdent, antifungal activities of n-hexadecanoic acid extracted from algae. South asian research journal of pharmaceutical sciences, 7, 125-127.
18. Gupta, k., taj, t., thansiya, b. & kamath, j. 2019. Pre-clinical evaluation of hepatoprotective activity of phytol in wistar albino rats. Ip international journal of comprehensive and advanced pharmacology, 4, 17-20.
19. Huang, c., cen, c., wang, c., zhan, h. & ding, x. 2014. Synergistic effects of colchicine combined with atorvastatin in rats with hyperlipidemia. Lipids in health and disease, 13, 1-6.
20. Islam, m. T., ali, e. S., uddin, s. J., shaw, s., islam, m. A., ahmed, m. I., chandra shill, m., karmakar, u. K., yarla, n. S., khan, i. N., billah, m. M., pieczynska, m. D., zengin, g., malainer, c., nicoletti, f., gulei, d., berindan-neagoe, i., apostolov, a., banach, m., yeung, W. K., el-demerdash, a., xiao, j., dey, p., yele, s., jóźwik, a., strzałkowska, n., marchewka, j., rengasamy, k. R. R., horbańczuk, j., kamal, m. A., mubarak, m. S., mishra, s. K., shilpi, j. A. & atanasov, a. G. 2018. Phytol: a review of biomedical activities. Food chem toxicol, 121, 82-94.
21. Islamiana, d., rafsanjani, i. S., pramaningtyas, m. D. & fauziyati, a. Effect of high-fat diet on systolic blood pressure in stz-induced diabetic adolescent sprague dawley rats. 4th international conference on sustainable innovation 2020–health science and nursing (icosihsn 2020), 2021. Atlantis press, 69-74.
22. Kalsait, r., khedekar, p., saoji, a. & bhusari, k. 2011. Role of c-reactive protein in the development of atherosclerosis in diet-induced lipidemia in albino rats. Tropical journal of pharmaceutical research, 10, 41-45.
23. Kassab, d. Y., sheeba, d., r, g., searan, w., abdalqader, m., kayarohanam, s., jamal, i., kumar janakiraman, a., soutallu janakiram, m. K. & bhupathyraaj, m. 2025. Evaluation of antihyperlipidemic activity of leaf extracts of rivea hypocrateriformis (desr.) In high-fat diet-induced hyperlipidemia rat model with focus on gene expression. International journal of nutrition, pharmacology, neurological diseases, 15, 82-91.
24. Kathak, r. R., sumon, a. H., molla, n. H., hasan, m., miah, r., tuba, h. R., habib, a. & ali, n. 2022. The association between elevated lipid profile and liver enzymes: a study on bangladeshi adults. Scientific reports, 12, 1711.
25. Kim, h., lim, d. H. & kim, y. 2021. Classification and prediction on the effects of nutritional intake on overweight/obesity, dyslipidemia, hypertension and type 2 diabetes mellitus using deep learning model: 4–7th korea national health and nutrition examination survey. International journal of environmental research and public health, 18, 5597.
26. Kittel, b., ruehl-fehlert, c., morawietz, g., klapwijk, j., elwell, m. R., lenz, b., o'sullivan, m. G., roth, d. R. & wadsworth, p. F. 2004. Revised guides for organ sampling and trimming in rats and mice--part 2. A joint publication of the rita and nacad groups. Exp toxicol pathol, 55, 413-31.
27. Kumar, p., singh, s. & ahmad, m. I. 2020. Synergistic effect of cinnamomum zeylanicum and murraya koenigii formulation for antiobesity and hypolipidemic activity on wistar albino rats. Advances in traditional medicine, 21.
28. Latifi, e., mohammadpour, a. A., h, b. F. & nourani, h. 2019. Antidiabetic and antihyperlipidemic effects of ethanolic ferula assa-foetida oleo-gum-resin extract in streptozotocin-induced diabetic wistar rats. Biomed pharmacother, 110, 197-202.
29. Layton, c. & suvarna, k. 2013. Bancroft's theory and practise of histological techniques (7th edition) (co-author).
30. Li, m., li, m., wang, l., li, m. & wei, j. 2023. Apiaceae medicinal plants: a review of traditional uses, phytochemistry, bolting and flowering, and controlling approaches.
31. Lozano, i., van der werf, r., bietiger, w., seyfritz, e., peronet, c., pinget, m., jeandidier, n., maillard, e., marchioni, e. & sigrist, s. 2016. High-fructose and high-fat diet-induced disorders in rats: impact on diabetes risk, hepatic and vascular complications. Nutrition & metabolism, 13, 1-13.
32. Mishor, e., amir, d., weiss, t., honigstein, d., weissbrod, a., livne, e., gorodisky, l., karagach, s., ravia, a., snitz, k., karawani, d., zirler, r., weissgross, r., soroka, t., endevelt-shapira, y., agron, s., rozenkrantz, l., reshef, n., furman-haran, e., breer, h., strotmann, j., uebi, t., ozaki, m. & sobel, n. 2021. Sniffing the human body volatile hexadecanal blocks aggression in men but triggers aggression in women. Sci adv, 7, eabg1530.
33. Mojarrad, s. 2020. Responses of liver and renal function markers against arjuna tree extract in induced hyperlipidemia rats. Issue s, 10.
34. Mosca, s., araújo, g., costa, v., correia, j., bandeira, a., martins, e., mansilha, h., tavares, m. & coelho, m. P. 2022. Dyslipidemia diagnosis and treatment: risk stratification in children and adolescents. Journal of nutrition and metabolism, 2022.
35. Nelson, r. H. 2012. Hyperlipidemia as a risk factor for cardiovascular disease. Primary care, 40, 195.
36. Nemoto, t., nakakura, t. & kakinuma, y. 2020. Elevated blood pressure in high-fat diet-exposed low birthweight rat offspring is most likely caused by elevated glucocorticoid levels due to abnormal pituitary negative feedback. Plos one, 15, e0238223.
37. Niknafs, a., rezvanfar, m., kamalinejad, m., latifi, s. A., almasi-hashiani, a. & salehi, m. 2021. The effect of a persian herbal medicine compound on the lipid profiles of patients with dyslipidemia: a randomized double-blind placebo-controlled clinical trial. Evidence-based complementary and alternative medicine, 2021, 1-9.
38. Panchal, s. K. & brown, l. 2011. Rodent models for metabolic syndrome research. J biomed biotechnol, 2011, 351982.
39. Pasavei, a. G., mohebbati, r., boroumand, n., ghorbani, a., hosseini, a., jamshidi, s. T. & soukhtanloo, m. 2020. Anti-hypolipidemic and anti-oxidative effects of hydroalcoholic extract of origanum majorana on the hepatosteatosis induced with high-fat diet in rats. The malaysian journal of medical sciences: mjms, 27, 57.
40. Pehlić, m., dumančić, s., radan, m., galić, j., gruica, b., marijan, s. & vulić, m. 2024. Untargeted urinary volatilomics reveals hexadecanal as a potential biomarker for preeclampsia. Int j mol sci, 25.
41. Pieroni, a., ahmed, h. & hamadamin, h. 2016. The spring has arrived: traditional wild vegetables gathered by yarsanis (ahl-e haqq) and sunni muslims in western hawraman, se kurdistan (iraq). Acta societatis botanicorum poloniae, 86.
42. Qi, y. & wang, x. 2023. The role of gut microbiota in high-fat-diet-induced diabetes: lessons from animal models and humans. Nutrients, 15, 922.
43. Sert, n. P. D., ahluwalia, a., alam, s., avey, m. T., baker, m., browne, w. J., clark, a., cuthill, i. C., dirnagl, u. & emerson, m. J. P. B. 2020. Reporting animal research: explanation and elaboration for the arrive guidelines 2.0. 18, 1-65.
44. Shaaban, m. T., ghaly, m. F. & fahmi, s. M. 2021. Antibacterial activities of hexadecanoic acid methyl ester and green-synthesized silver nanoparticles against multidrug-resistant bacteria. J basic microbiol, 61, 557-568.
45. Sousa, r. M. O. F., cunha, a. C. & fernandes-ferreira, m. 2021. The potential of apiaceae species as sources of singular phytochemicals and plant-based pesticides. Phytochemistry, 187, 112714.
46. Spanoudaki, m., chrysafi, m., papadopoulou, s. K., tsourouflis, g., pritsa, a. & giaginis, c. 2024. Naturally occurring compounds targeting peroxisome proliferator receptors: potential molecular mechanisms and future perspectives for promoting human health. Applied sciences, 14, 9994.
47. Sunil, b. & ashraf, a. P. 2020. Dyslipidemia in pediatric type 2 diabetes mellitus. Current diabetes reports, 20, 1-9.
48. Suvarna, s. K. L., christopher; bancroft, john d. 2024. Bancroft's theory and practice of histological techniques, elsevier.
49. Tang, n., ma, j., tao, r., chen, z., yang, y., he, q., lv, y., lan, z. & zhou, j. 2022. The effects of the interaction between bmi and dyslipidemia on hypertension in adults. Scientific reports, 12, 927.
50. Thiviya, p., gunawardena, n., gamage, a., madhujith, t. & merah, o. 2022. Apiaceae family as a valuable source of biocidal components and their potential uses in agriculture. Horticulturae, 8, 614.
51. Wang, y., yu, h. & he, j. 2020. Role of dyslipidemia in accelerating inflammation, autoimmunity, and atherosclerosis in systemic lupus erythematosus and other autoimmune diseases. Discovery medicine, 30, 49-56.
52. Wilkinson, m. & shapiro, m. 2024. Immune-mediated inflammatory diseases, dyslipidemia, and cardiovascular risk: a complex interplay. Arteriosclerosis, thrombosis, and vascular biology, 44, 2396-2406.
53. Wojcikowski, k. & gobe, g. 2014. Animal studies on medicinal herbs: predictability, dose conversion and potential value. Phytother res, 28, 22-7.
54. Xing, l., jing, l., tian, y., yan, h., zhang, b., sun, q., dai, d., shi, l., liu, d., yang, z. & liu, s. 2020. Epidemiology of dyslipidemia and associated cardiovascular risk factors in northeast china: a cross-sectional study. Nutrition, metabolism and cardiovascular diseases, 30, 2262-2270.
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