Table 3.

Effects of β-caryophyllene against diabetic complications.

Experimental Models	BCP Dose/Concentration/Period	Diabetic Complications	Effects and Mechanisms of BCP	References
Human mesangial cells	6.25, 12.5 and 25 μM for 1 h and then cells stimulated with high-glucose for 24 h	Diabetic nephropathy	▪inhibited cell proliferation, ROS and NADPH oxidase (NOX) 2/4 expression ▪lowered TNF-α, IL-1β, -6 levels ▪suppressed fibronectin & collagen IV ▪inhibited NF-κB and Nrf2 activation	[117]
STZ 40 mg/kg, i.p. at wk 1 (induction), STZ 120 mg/kg at wk 3, (reinforcement) to BALB/c female mice	10 mg/kg/60 μL, 45 days	Diabetic neuropathic pain	▪reduced blood glucose and increased insulin levels ▪alleviated diabetic neuropathy pain ▪reduced substance P and pro-inflammatory cytokines	[115]
B16F10 melanoma cells-induced tumor and lymph node metastasis in high-fat diet (60 kcal%) C57BL/6N mice	0, 0.15 or 0.3% for 16 weeks with HFD	Diabetes associated cancer	▪inhibited weight gain, tumor growth and metastasis ▪inhibited cell cycle progression, cell survival, angiogenesis and lymphangiogenesis in tumors ▪inhibited lipids and cytokine secretion	[123]
Mouse femoral tissues derived bone marrow cells	0.1–100 μM	Diabetes associated osteoporosis	▪stimulated osteoblast mineralization ▪inhibited adipogenesis by activating PPAR and osteoclastogenesis ▪inhibited TNF-α and NF-κB	[122]
CT26 colorectal tumor cells exposed to high-glucose, and CT26 cells transplanted in STZ (100 mg/kg)-induced DM in male Balb/c mice	50 μM for 48 h in vitro and 200 mg/kg, P.O to mice for 10 days	Diabetes associated colorectal cancer	▪reduced ART1 overexpression ▪modulated glycolysis and energy metabolism ▪upregulated protein kinase B/mTOR/c-Myc pathway & glycolytic enzymes expression ▪suppressed proliferation and enhanced apoptosis of cancer cells	[118]
Distal symmetric polyneuropathy in patients with DM	Diet supplement containing BCP, myrrh, carnosic acid	Diabetic polyneuropathy	▪beneficial in painful diabetic distal symmetric sensory-motor neuropathy ▪tolerated with no side effects	[116]

STZ, Streptozotocin; HFD, high fat diet; DM, diabetes mellitus; ROS, reactive oxygen species; NADPH, nicotinamide adenine dinucleotide phosphate; PPAR, Peroxisome proliferator-activated receptor.