Citrus hystrix DC for Metabolic Disorders: Comparison
Please note this is a comparison between Version 2 by Camila Xu and Version 1 by Yusof Kamisah.

Metabolic disorder, which includes hypertension, diabetes mellitus, dyslipidemia, and obesity, represents a major global health concern due to increased morbidity and mortality. It occurs due to disturbance in normal metabolic process leading to redox and energy imbalance. Metabolic disorder, which includes hypertension, diabetes mellitus, dyslipidemia, and obesity, represents a major global health concern due to increased morbidity and mortality. It occurs due to disturbance in normal metabolic process leading to redox and energy imbalance.

  • kaffir lime
  • diabetes mellitus
  • hypertension
  • dyslipidemia
  • obesity

1. Introduction

Metabolic disorder, which includes hypertension, diabetes mellitus, dyslipidemia, and obesity, represents a major global health concern due to increased morbidity and mortality. It occurs due to disturbance in normal metabolic process leading to redox and energy imbalance [1]. The incidence of metabolic disorders increased during the COVID-19 lockdown due to lack of activities and physical exercise, as well as increased intake of homemade food rich in fat [2]. Many factors contribute to the development of this disorder, including an unhealthy diet, sedentary lifestyle, lack of physical exercise, and smoking [1]. Several therapeutic goals have been established to educate high-risk individuals to modify their lifestyle to slow down or prevent the progression of metabolic disorders.
Oxidative stress and inflammation play a major role in the development and progression of metabolic disorders [1,3][1][3]. Therefore, it has been theorized that plant extracts with antioxidant and anti-inflammatory properties could have beneficial effects on patients with metabolic disorders. Animal studies have shown that plant extracts such as those of Parkia speciosa Hassk., which is rich in flavonoids, confer protective effects against hypertension [4], while Ganoderma lucidum proteoglycans protect against diabetes [5], and açaí seed extract rich in proanthocyanidins protects against dyslipidemia [6]. Citrus hystrix DC extract has shown protective effects against diabetes [7], hypertension [8], and dyslipidemia [9].
Citrus hystrix (Figure 1), also known as kaffir lime or makrut lime, also goes by the following names: Citrus auraria Michel, Citrus echinata SaintLager, Citrus hyalopulpa Tanaka, and Citrus kerrii (Swingle) Tanaka [10]. It is a flowering, shrubby plant in the family Rutaceae that grows 3 to 6 m high and is indigenous to tropical Southeast Asia, southern China, and northeastern India [10,11][10][11]. It bears green, warty, and bumpy fruits. The leaves and fruits are often used as spices in Asian cooking [12]. Many bioactive compounds from the plant have been studied for their therapeutic potential in improving the symptoms of metabolic disorders in animal studies.
Figure 1.
The plant of
Citrus hystrix
DC.

2. Traditional Medicinal Uses

The fruits, leaves, and rind of C. hystrix are the most common parts traditionally used to reduce the severity of certain illnesses (Table 1). The fruits are used for the treatment of stomachache by hilly Tripura tribes in northeastern India [11], while the leaves and fruits are both used in steam-bathing for postpartum mothers, to relieve headache, rheumatism, fever, and to treat diabetes mellitus in North Sumatra, Indonesia [13]. In Malaysia, the fruits are used in hair shampoo to decrease dandruff and to promote hair growth [10]. The leaves and fruits are also used to boost sexual performance [13] and to treat hypertension, heart disease, and diarrhea [14,15][14][15].
Table 1.
Traditional medicinal uses of
C. hystrix
.

3. Phytochemical Properties

Various phytochemical compounds have been detected in the leaves, roots, fruits, and rind of C. hystrix (Table 2). Terpenoids are the major compounds identified in the leaves of the plant, while coumarins are predominantly found in the roots. The leaves also contain phytosterol and flavonoids. The rind extract, which is rich in flavonoids, possesses high antioxidant. It also demonstrates lipase-inhibiting activity which is beneficial for the treatment of obesity, angiotensin-converting enzyme-inhibiting property for the management of hypertension, moderate inhibiting activity against α-amylase and α-glucosidase which could be useful in diabetes, as well as inhibitions against acetylcholinesterase, butyrylcholinesterase, and β-secretase-1 which are favorable in the treatment of Alzheimer’s disease [19].
Table 2.
Phytochemical compounds in various parts of
C. hystrix
.

References

  1. Su, Z.; Guo, Y.; Huang, X.; Feng, B.; Tang, L.; Zheng, G.; Zhu, Y. Phytochemicals: Targeting mitophagy to treat metabolic disorders. Front. Cell. Dev. Biol. 2021, 9, 686820.
  2. Auriemma, R.S.; Pirchio, R.; Liccardi, A.; Scairati, R.; Del Vecchio, G.; Pivonello, R.; Colao, A. Metabolic syndrome in the era of COVID-19 outbreak: Impact of lockdown on cardiometabolic health. J. Endocrinol. Investig. 2021, 44, 2845–2847.
  3. Torres, S.; Medina, R.B.; Vasallo Morillas, M.I.; Isla, M.I.; Gauffin-Cano, P. Editorial: Functional foods and bioactive food ingredients in prevention and alleviation of metabolic syndrome. Front. Nutr. 2021, 8, 788941.
  4. Kamisah, Y.; Zuhair, J.S.F.; Juliana, A.H.; Jaarin, K. Parkia speciosa empty pod prevents hypertension and cardiac damage in rats given N(G)-nitro-l-arginine methyl ester. Biomed. Pharmacother. 2017, 96, 291–298.
  5. Yu, F.; Wang, Y.; Teng, Y.; Yang, S.; He, Y.; Zhang, Z.; Yang, H.; Ding, C.F.; Zhou, P. Interaction and inhibition of a Ganoderma lucidum proteoglycan on PTP1B activity for anti-diabetes. ACS Omega 2021, 6, 29804–29813.
  6. de Moraes Arnoso, B.J.; Magliaccio, F.M.; de Araújo, C.A.; de Andrade Soares, R.; Santos, I.B.; de Bem, G.F.; Fernandes-Santos, C.; Ognibene, D.T.; de Moura, R.S.; Resende, A.C.; et al. Acai seed extract (ASE) rich in proanthocyanidins improves cardiovascular remodeling by increasing antioxidant response in obese high-fat diet-fed mice. Chem. Biol. Interact. 2021, 351, 109721.
  7. Umran, N.S.S.; Mohamed, S.; Lau, S.F.; Mohd Ishak, N.I. Citrus hystrix leaf extract attenuated diabetic-cataract in STZ-rats. J. Food Biochem. 2020, 44, e13258.
  8. Siti, H.N.; Kamisah, Y.; Nur Iliyani, M.I.; Mohamed, S.; Jaarin, K. Citrus leaf extract reduces blood pressure and vascular damage in repeatedly heated palm oil diet-induced hypertensive rats. Biomed. Pharmacother. 2017, 87, 451–460.
  9. Nugraheni, D.M.; Kurniati, I.D.; Deliara, H.; Kusuma, M.A. Kadar LDL tikus betina setelah pemberian ekstrak kulit jeruk purut (Citrus hystrix). Herb. Med. J. 2020, 3, 39–46.
  10. Lim, T.K. Citrus hystrix. In Edible Medicinal and Non-Medicinal Plants: Fruits; Springer Science + Business Media B.V.: Dordrecht, The Netherlands, 2012; Volume 4, pp. 634–643.
  11. Das, S.C.; Prakash, J.; Deb, A.K.; Biswas, T. Medicinal value of underutilized fruits in hilly Tripura. Acta Hortic. 2013, 972, 135–141.
  12. Md Othman, S.N.A.; Hassan, M.A.; Nahar, L.; Basar, N.; Jamil, S.; Sarker, S.D. Essential oils from the Malaysian citrus (Rutaceae) medicinal plants. Medicines 2016, 3, 13.
  13. Silalahi, M.; Nisyawati, N. An ethnobotanical study of traditional steam-bathing by the Batak people of North Sumatra, Indonesia. Pac. Conserv. Biol. 2018, 25, 266–282.
  14. Abirami, A.; Nagarani, G.; Siddhuraju, P. The medicinal and nutritional role of underutilized citrus fruit Citrus hystrix (Kaffir lime): A review. Drug Invent. Today 2014, 6, 1–5.
  15. Neamsuvan, O.; Komonhiran, P.; Boonming, K. Medicinal plants used for hypertension treatment by folk healers in Songkhla province, Thailand. J. Ethnopharmacol. 2018, 214, 58–70.
  16. Yabesh, J.E.; Prabhu, S.; Vijayakumar, S. An ethnobotanical study of medicinal plants used by traditional healers in silent valley of Kerala, India. J. Ethnopharmacol. 2014, 154, 774–789.
  17. Alsarhan, A.; Sultana, N.; Kadir, M.R.A.; Aburjai, T. Ethnopharmacological survey of medicinal plants in Malaysia, the Kangkar Pulai region. Int. J. Pharmacol. 2012, 8, 679–686.
  18. Anuchapreeda, S.; Anzawa, R.; Viriyaadhammaa, N.; Neimkhum, W.; Chaiyana, W.; Okonogi, S.; Usuki, T. Isolation and biological activity of agrostophillinol from kaffir lime (Citrus hystrix) leaves. Bioorg. Med. Chem. Lett. 2020, 30, 127256.
  19. Suttisansanee, U.; Thiyajai, P.; Chalermchaiwat, P.; Wongwathanarat, K.; Pruesapan, K.; Charoenkiatkul, S.; Temviriyanukul, P. Phytochemicals and in vitro bioactivities of aqueous ethanolic extracts from common vegetables in Thai food. Plants 2021, 10, 1563.
  20. Chanthaphon, S.; Chanthachum, S.; Hongpattarakere, T. Antimicrobial activities of essential oils and crude extracts from tropical Citrus spp. against food-related microorganisms. Songklanakarin J. Sci. Technol. 2008, 30, 125–131.
  21. Dertyasasa, E.D.; Tunjung, W.A.S. Volatile organic compounds of kaffir lime (Citrus Hystrix DC.) leaves fractions and their potency as traditional medicine. Biosci. Biotech. Res. Asia 2017, 14, 1235–1250.
  22. Anuchapreeda, S.; Chueahongthong, F.; Viriyaadhammaa, N.; Panyajai, P.; Anzawa, R.; Tima, S.; Ampasavate, C.; Saiai, A.; Rungrojsakul, M.; Usuki, T.; et al. Antileukemic cell proliferation of active compounds from kaffir lime (Citrus hystrix) leaves. Molecules 2020, 25, 1300.
  23. Buakaew, W.; Pankla Sranujit, R.; Noysang, C.; Thongsri, Y.; Potup, P.; Nuengchamnong, N.; Suphrom, N.; Usuwanthim, K. Phytochemical constituents of Citrus hystrix DC. leaves attenuate inflammation via NF-κB signaling and NLRP3 inflammasome activity in macrophages. Biomolecules 2021, 11, 105.
  24. Panthong, K.; Srisud, Y.; Rukachaisirikul, V.; Hutadilok-Towatana, N.; Voravuthikunchai, S.P.; Tewtrakul, S. Benzene, coumarin and quinolinone derivatives from roots of Citrus hystrix. Phytochemistry 2013, 88, 79–84.
  25. Murakami, A.; Nakamura, Y.; Koshimizu, K.; Ohigashi, H. Glyceroglycolipids from Citrus hystrix, a traditional herb in Thailand, potently inhibit the tumor-promoting activity of 12-O-tetradecanoylphorbol 13-acetate in mouse skin. J. Agric. Food Chem. 1995, 43, 2779–2783.
  26. Ching, L.S.; Mohamed, S. Alpha-Tocopherol content in 62 edible tropical plants. J. Agric. Food Chem. 2001, 49, 3101–3105.
  27. Butryee, C.; Sungpuag, P.; Chitchumroonchokchai, C. Effect of processing on the flavonoid content and antioxidant capacity of Citrus hystrix leaf. Int. J. Food Sci. Nutr. 2009, 60, 162–174.
  28. Roowi, S.; Crozier, A. Flavonoids in tropical citrus species. J. Agric. Food Chem. 2011, 59, 12217–12225.
  29. Ito, C.; Fujiwara, K.; Kajita, M.; Ju-Ichi, M.; Takemura, Y.; Suzuki, Y.; Tanaka, K.; Omura, M.; Furukawa, H. New coumarins from citrus plants. Chem. Pharm. Bull. 1991, 39, 2509–2513.
  30. Youkwan, J.; Sutthivaiyakit, S.; Sutthivaiyakit, P. Citrusosides A–D and furanocoumarins with cholinesterase inhibitory activity from the fruit peels of Citrus hystrix. J. Nat. Prod. 2010, 73, 1879–1883.
  31. Sun, S.; Phrutivorapongkul, A.; Dibwe, D.F.; Balachandran, C.; Awale, S. Chemical constituents of Thai Citrus hystrix and their antiausterity activity against the PANC-1 human pancreatic cancer cell line. J. Nat. Prod. 2018, 81, 1877–1883.
  32. Sadasivam, M.; Kumarasamy, C.; Thangaraj, A.; Govindan, M.; Kasirajan, G.; Vijayan, V.; Devadasan, V.; Chia-Her, L.; Madhusudhanan, G.R.; Ramaraj, T.; et al. Phytochemical constituents from dietary plant Citrus hystrix. Nat. Prod. Res. 2018, 32, 1721–1726.
  33. Seeka, C.; Sutthivaiyakit, P.; Youkwan, J.; Hertkorn, N.; Harir, M.; Schmitt-Kopplin, P.; Sutthivaiyakit, S. Prenylfuranocoumarin-HMGA-flavonol glucoside conjugates and other constituents of the fruit peels of Citrus hystrix and their anticholinesterase activity. Phytochemistry 2016, 127, 38–49.
  34. Shaha, R.K.; Punichelvana, Y.N.A.P.; Afandi, A. Optimized extraction condition and characterization of pectin from kaffir lime (Citrus hystrix). Res. J. Agric. Forest. Sci. 2013, 1, 1–11.
  35. Warsito, W.; Palungan, M.H.; Utomo, E.P. Profiling study of the major and minor components of kaffir lime oil (Citrus hystrix DC.) in the fractional distillation process. Pan Afr. Med. J. 2017, 27, 282.
  36. Waikedre, J.; Dugay, A.; Barrachina, I.; Herrenknecht, C.; Cabalion, P.; Fournet, A. Chemical composition and antimicrobial activity of the essential oils from New Caledonian Citrus macroptera and Citrus hystrix. Chem. Biodivers. 2010, 7, 871–877.
  37. Hien, T.T.; Quyen, N.T.C.; Truc, T.T.; Quan, P.M. Evaluate the chemical composition of kaffir lime (Citrus hystrix) essential oil using the classical method. IOP Conf. Ser. Mater. Sci. Eng. 2020, 991, 012014.
  38. Baccati, C.; Gibernau, M.; Paoli, M.; Ollitrault, P.; Tomi, F.; Luro, F. Chemical variability of peel and leaf essential oils in the citrus subgenus papeda (Swingle) and few relatives. Plants 2021, 10, 1117.
  39. Norkaew, O.; Pitija, K.; Pripdeevech, P.; Sookwong, P.; Wongporncha, S. Supercritical fluid extraction and gas chromatographic-mass spectrometric analysis of terpenoids in fresh kaffir lime leaf oil. Chiang Mai J. Sci. 2013, 40, 240–247.
  40. Kordali, S.; Kotan, R.; Cakir, A. Screening of antifungal activities of 21 oxygenated monoterpenes in-vitro as plant disease control agents. Allelopathy J. 2007, 19, 373–392.
  41. Shepard, B.D. Sex differences in diabetes and kidney disease: Mechanisms and consequences. Am. J. Physiol. Renal Physiol. 2019, 317, F456–F462.
  42. Luc, K.; Schramm-Luc, A.; Guzik, T.J.; Mikolajczyk, T.P. Oxidative stress and inflammatory markers in prediabetes and diabetes. J. Physiol. Pharmacol. 2019, 70, 809–824.
  43. Abirami, A.; Nagarani, G.; Siddhuraju, P. Measurement of functional properties and health promoting aspects-glucose retardation index of peel, pulp and peel fiber from Citrus hystrix and Citrus maxima. Bioact. Carbohydr. Diet. Fibre 2014, 4, 16–26.
  44. Irawaty, W.; Ayucitra, A. Assessment on antioxidant and in vitro antidiabetes activities of different fractions of Citrus hystrix peel. Int. Food Res. J. 2018, 25, 2467–2477.
  45. Abirami, A.; Nagarani, G.; Siddhuraju, P. In vitro antioxidant, anti-diabetic, cholinesterase and tyrosinase inhibitory potential of fresh juice from Citrus hystrix and C. maxima fruits. Food Sci. Hum. Wellness 2014, 3, 16–25.
  46. Setyabudi, C.; Tanda, S.; Santosa, W.I.; Soetaredjo, F.E. Studi in vitro ekstrak kulit jeruk purut untuk aplikasi terapi diabetes mellitus. J. Ilm. Widya Tek. 2015, 14, 15–19.
  47. Rekasih, M.; Muhandri, T.; Safithri, M.; Wijaya, C.H. Antihyperglycemic Activity of Java tea-based functional drink loaded chitosan nanoparticle in streptozotocin-induced diabetic rats. Hayati J. Biosci. 2021, 28, 212–222.
  48. Janiak, M.C. Of starch and spit. Elife 2019, 8, e47523.
  49. Saleh, M.S.M.; Jalil, J.; Mustafa, N.H.; Ramli, F.F.; Asmadi, A.Y.; Kamisah, Y. UPLC-MS-based metabolomics profiling for α-glucosidase inhibiting property of Parkia speciosa pods. Life 2021, 11, 78.
  50. Crespo, M.E.; Gálvez, J.; Cruz, T.; Ocete, M.A.; Zarzuelo, A. Anti-inflammatory activity of diosmin and hesperidin in rat colitis induced by TNBS. Planta Med. 1999, 65, 651–653.
  51. Siti, H.N.; Jalil, J.; Asmadi, A.Y.; Kamisah, Y. Rutin modulates MAPK Pathway differently from quercetin in angiotensin ii-induced H9c2 cardiomyocyte hypertrophy. Int. J. Mol. Sci. 2021, 22, 5063.
  52. Zhang, H.L.; Wu, X.Y.; Mi, J.; Peng, Y.J.; Wang, Z.G.; Liu, Y.; Wu, X.L.; Gao, Y. A new anti-inflammatory alkaloid from roots of Heracleum dissectum. Chem. Biodivers. 2017, 14, e1700184.
  53. Koysu, P.; Genc, N.; Elmastas, M.; Aksit, H.; Erenler, R. Isolation, identification of secondary metabolites from Salvia absconditiflora and evaluation of their antioxidative properties. Nat. Prod. Res. 2019, 33, 3592–3595.
  54. Tirumani, P.; Venu, S.; Sridhar, G.; Praveen Kumar, M.; Rajashekhar, A.V.; Naga Raju, T. Delaying of cataract through intervention of Hemidesmus indicus in STZ induced diabetic rats. Nat. Prod. Res. 2018, 32, 1295–1298.
  55. Singh, A.; Bodakhe, S.H. Biochemical evidence indicates the preventive effect of resveratrol and nicotinamide in the treatment of STZ-induced diabetic cataract. Curr. Eye Res. 2021, 46, 52–63.
  56. Jang, D.J.; Kim, S.T.; Oh, E.; Lee, K. Enhanced oral bioavailability and antiasthmatic efficacy of curcumin using redispersible dry emulsion. BioMed Mater. Eng. 2014, 24, 917–930.
  57. Gumprecht, J.; Domek, M.; Lip, G.Y.H.; Shantsila, A. Invited review: Hypertension and atrial fibrillation: Epidemiology, pathophysiology, and implications for management. J. Hum. Hypertens. 2019, 33, 824–836.
  58. Siti, H.N.; Kamisah, Y.; Kamsiah, J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascul. Pharmacol. 2015, 71, 40–56.
  59. Khalid, N.M.; Babji, A.S. Antioxidative and antihypertensive activities of selected Malaysian ulam (salad), vegetables and herbs. J. Food Res. 2018, 7, 27–37.
  60. Tejpal, S.; Wemyss, A.M.; Bastie, C.C.; Klein-Seetharaman, J. Lemon extract reduces angiotensin converting enzyme (ACE) Expression and activity and increases insulin sensitivity and lipolysis in mouse adipocytes. Nutrients 2020, 12, 2348.
  61. Jaarin, K.; Mustafa, M.R.; Leong, X.F. The effects of heated vegetable oils on blood pressure in rats. Clinics 2011, 6, 2125–2132.
  62. Ng, C.Y.; Kamisah, Y.; Faizah, O.; Jaarin, K. The role of repeatedly heated soybean oil in the development of hypertension in rats: Association with vascular inflammation. Int. J. Exp. Pathol. 2012, 93, 377–387.
  63. Suhaimi, N.H.; Zuhair, J.S.F.; Azlan, M.A.; Juliana, A.H.; Mustazil, M.N.M.; Zainalabidin, S.; Jaarin, K.; Mohamed, S.; Kamisah, Y. Addition of citrus leaf extract into frying oil prevents hypertension and improves vascular reactivity in heated oil-fed rats. J. Food Nutr. Res. 2020, 8, 417–423.
  64. Sukalingam, K.; Jaarin, K.; Saad, Q.H.M.; Mohamed, S.; Othman, F. Consumption of ADD-X and repeatedly heated palm oil on the blood pressure and oxidative stress markers in ovarectemized rats. Int. J. Pharmacol. 2016, 12, 514–522.
  65. Adam, S.K.; Sulaiman, N.A.; Mat Top, A.G.; Jaarin, K. Heating reduces vitamin E content in palm and soy oils. J. Biochem. Mol. Biol. 2007, 5, 76–79.
  66. Siti, H.N.; Kamisah, Y.; Mohamed, S.; Jaarin, K. Effects of citrus leaf extract on aortic vascular reactivity in hypertensive rats fed repeatedly heated vegetable oil. Appl. Physiol. Nutr. Metab. 2019, 44, 373–380.
  67. Sukalingam, K.; Jaarin, K.; Saad, Q.H.M.; Mohamed, S.; Othman, F. Effect of Rutacea plant extract (ADD-X) on inflammatory biomarkers, cardiac ldl, troponin t and histological changes in ovariectomized rats fed with heated palm oil. Int. J. Toxicol. Pharmacol. Res. 2016, 8, 223–231.
  68. Li, C.J.; Barkath, A.A.; Abdullah, M.Z.; Lingkan, N.; Ismail, N.H.M.; Pauzi, S.H.M.; Kamisah, Y.; Qodriyah, H.M.S.; Jaarin, K.; Mohamed, S.; et al. The effects of citrus leaf extract on renal oxidative stress, renal function and histological changes in rats fed with heated palm oil. Biomed. Pharmacol. J. 2019, 12, 363–373.
  69. Imai, T.; Morita, T.; Shindo, T.; Nagai, R.; Yazaki, Y.; Kurihara, H.; Suematsu, M.; Katayama, S. Vascular smooth muscle cell-directed overexpression of heme oxygenase-1 elevates blood pressure through attenuation of nitric oxide induced vasodilation in mice. Circ. Res. 2001, 89, 55–62.
  70. Shen, J.; Yip, S.; Wang, Z.; Wang, W.; Xing, D.; Du, L. Brazilein induced contraction of rat arterial smooth muscle involves activation of Ca2+ entry and ROK, ERK pathways. Eur. J. Pharmacol. 2008, 580, 366–371.
  71. Lüneburg, N.; Harbaum, L.; Hennigs, J.K. The endothelial ADMA/NO pathway in hypoxia-related chronic respiratory diseases. Biomed Res Int. 2014, 2014, 501612.
  72. Muñoz-Durango, N.; Fuentes, C.A.; Castillo, A.E.; González-Gómez, L.M.; Vecchiola, A.; Fardella, C.E.; Kalergis, A.M. Role of the renin-angiotensin-aldosterone system beyond blood pressure regulation: Molecular and cellular mechanisms involved in end-organ damage during arterial hypertension. Int. J. Mol. Sci. 2016, 17, 797.
  73. Gui, J.S.; Mustafa, N.; Jalil, J.; Jubri, Z.; Kamisah, Y. Modulation of NOX4 and MAPK signalling pathways by Parkia speciosa empty pods in H9c2 cardiomyocytes exposed to H2O2. Indian J. Pharm. Sci. 2019, 81, 1029–1035.
  74. Gao, L.; Yuan, P.; Zhang, Q.; Fu, Y.; Hou, Y.; Wei, Y.; Zheng, X.; Feng, W. Taxifolin improves disorders of glucose metabolism and water-salt metabolism in kidney via PI3K/AKT signaling pathway in metabolic syndrome rats. Life Sci. 2020, 263, 118713.
  75. Kumar, V.; Kurth, T.; Zheleznova, N.N.; Yang, C.; Cowley, A.W., Jr. NOX4/H(2)O(2)/mTORC1 pathway in salt-induced hypertension and kidney injury. Hypertension 2020, 76, 133–143.
  76. Karr, S. Epidemiology and management of hyperlipidemia. Am. J. Manag. Care 2017, 23, S139–S148.
  77. Deliara, H.; Kartikadewi, A.; Nugraheni, D.M. Kaffir lime peel ethanol extract (Citrus hystrix) as a cholesterol reducing agent: In vivo study. Med. Art. 2020, 2, 1–9.
  78. State-Ease. Least Significant Difference (LSD). Available online: https://www.statease.com/docs/v11/contents/model-graphs/least-significant-difference-bars/ (accessed on 21 December 2021).
  79. Zajmi, A.; Ramli, L.H.; Al-Abd, N.; Othman, Z. Anti-hyperlipidemia activity of key lime (Citrus aurantifolia) and kaffir lime (Citrus hystrix) peel extracts on high fat diet induced hyperlipidemic rats. Solid State Tech. 2020, 63, 2925–2932.
  80. Watanabe, D.; Kerakawati, R.; Morita, T.; Nakamura, T.; Ueno, K.; Kumamoto, T.; Nakanishi, W.; Ishikawa, T.; Uzawa, J.; Seki, H.; et al. Isolation of β-sitosterol and digalactopyranosyl-diacylglyceride from Citrus hystrix, a Thai traditional herb, as pancreatic lipase inhibitors. Heterocycles 2009, 78, 1497–1505.
  81. Tirawanchai, N.; Kengkoom, K.; Isarangkul, D.; Burana-Osot, J.; Kanjanapruthipong, T.; Chantip, S.; Phattanawasin, P.; Sotanaphun, U.; Ampawong, S. A combination extract of kaffir lime, galangal, and lemongrass maintains blood lipid profiles, hepatocytes, and liver mitochondria in rats with nonalcoholic steatohepatitis. Biomed. Pharmacother. 2020, 124, 109843.
  82. de la Garza, A.L.; Milagro, F.I.; Boque, N.; Campión, J.; Martínez, J.A. Natural inhibitors of pancreatic lipase as new players in obesity treatment. Planta Med. 2011, 77, 773–785.
  83. Piyachaturawat, P.; Glinsukon, T.; Chanjarunee, A. Antifertility effect of Citrus hystrix DC. J. Ethnopharmacol. 1985, 13, 105–110.
  84. Koh, D.; Ong, C.N. Phytophotodermatitis due to the application of citrus hystrix as a folk remedy. Br. J. Dermatol. 1999, 140, 737–738.
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