Potential Therapeutic Effects of Citrus hystrix DC and Its Bioactive Compounds on Metabolic Disorders

Abstract

Metabolic disorders like diabetes mellitus, hypertension, dyslipidemia, and obesity are major medical problems globally. The incidence of these disorders has increased tremendously in recent years. Studies have demonstrated that plants with antioxidant and anti-inflammatory properties have beneficial effects on these disorders. One of these plants is Citrus hystrix DC, commonly known as kaffir lime. This review aims to present updates on the progress of research regarding the use of C. hystrix in metabolic disorders. Phytochemical compounds, including β-pinene, sabinene, citronellal, and citronellol, have been detected in the plant; and its extract exhibited potential antidiabetic, antihyperlipidemic and anti-obesity activity, as well as prevention of development of hypertension. These beneficial properties may be attributable to the presence of bioactive compounds which have therapeutic potential in treating these metabolic disorders. The compounds have the potential to be developed as candidate drugs. This review will assist in validating the regulatory role of the extract and its bioactive compounds on metabolic disorders, thus expediting future research in the area.

Keywords: diabetes mellitus; dyslipidemia; hypertension; kaffir lime; obesity.

Figure 1

The plant of Citrus hystrix DC.

Figure 2

The flow of literature search.

Figure 3

Molecular structure of major phytochemical compounds in C. hystrix.

Figure 4

Possible sites of action of C. hystrix and its bioactive compounds in diabetes. PGE2, prostaglandin E2; TBARS, thiobarbituric acid reactive substance; TNF-α, tumor necrosis factor-α; VEGF, vascular endothelial growth factor; →, induces, → (with −), inhibits.

Figure 5

Possible sites of action of C. hystrix extract in ameliorating hypertension. AA, arachidonic acid; ACE, angiotensin-converting enzyme; ACh, acetylcholine; AD-R, adrenergic receptor; Ang I, angiotensin I, Ang II; angiotensin II; AT1R, angiotensin II type 1 receptor; cAMP, cyclic adenosine monoamine phosphate; cGMP, cyclic guanosine monophosphate; COX, cyclooxygenase; eNOS, endothelial nitric oxide synthase; ER, endoplasmic reticulum; GPx, glutathione peroxidase; FRx, glutathione reductase; GSSG, glutathione disulfide; GSH, reduced glutathione; GTP, guanosine-5′-triphosphate; HO-1, heme oxygenase-1; L-Arg, L-arginine; NF-κB, nuclear factor kappa-B; M-R, muscarinic receptor; NO, nitric oxide; PG, prostaglandin; PGI2, prostacyclin; ROS, reactive oxygen species; RyR, ryanodine receptor; SERCA, sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase; sGC, soluble guanylate cyclase; SOD, superoxide dismutase; TNF-α, tumor necrosis factor- α; TNFR, tumor necrosis factor receptor; TXB2, thromboxane B2; VCAM, vascular cell adhesion molecule; +, activates; --, inhibits.

Figure 6

Possible sites of action of C. hystrix extract and its bioactive compounds in lipid metabolism. ApoA-1, apolipoprotein A-1; CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; FFA, free fatty acid; HDL, high-density lipoprotein; HMG-CoA, 3-hydroxy-3-methylglutaryl-coenzyme A; LDL, low-density lipoprotein; LDL-R, low-density lipoprotein receptor; LPL, lipoprotein lipase; TG, triglyceride; VLDL, very-low-density lipoprotein; →, conversion or movement; --, inhibits.