Table 1.

Phytochemical-based nanoformulations for management of metabolic syndrome (MetS)

Phytochemical	Nanoformulation	Disorder	Cellular/animal model	Dose	Size	Outcome	Reference
Curcumin	PBLG-PEG-PBLG	Diabetic cardiomyopathy	Diabetic rats and H9C2 cells	20 mg/kg	30 nm	↑H2S, ↑CaSR, ↑CSE, ↑CaM	77
	CNPs @GMs/hydrogel	Diabetic wound	STZ-induced diabetic rats		4 to 8 µm	↑GSH ↓ROS	84
	SNEDDS	Diabetic neuropathy	STZ-induced diabetic rats	66.7 mg/kg	170 nm	↓TNF-α ↓IL-6	78
	PLGA-PVA polymers	Diabetic cataract	STZ-induced diabetic cataract model	2 mg/day	282±5.72 nm	↓VEGF ↑cellular uptake, bioavailability	79
	Pluronic nanomicelles	STZ-induced diabetes	STZ-induced diabetic rats	100 mg/kg	333±6 nm	↑Pdx-1 and NKx6.1	80
	PLGA-based NPs with Q10	Diabetes complications	STZ-induced diabetic rats	100 mg/kg	237±6 nm	↓CRP, IL-6, total cholesterol, ↓plasma triglycerides ↑HDL	81
	Curcumin nanoemulsion	Hypertension and hypercholesterolemia	In vitro study		42.93±29.85 nm	Inhibition of HMGR along with ACE	65
PEGMA-DMAEMA-MAO	Diabetic peripheral neuropathy	STZ-induced diabetic rats	4 mg/kg		↓IL-1β ↓p-AKt P2Y12 receptor on SGCs in the DRG	83
Capsicum oleoresin	Nanoemulsion	Obesity	High-fat (HF)-diet-induced obesity in rats	0.1 mL/80 g body weight	20–50 nm	↓Adipogenic gene expression ↑PPAR-α, UCP2 and CPT-1α	90
Alginate double-layer nanoemulsion	Obesity	HF-diet-induced obesity in rats and 3T3-L1 cell line	1,000 ng/mL		↓mRNA levels of PPAR-γ ↓fatty acid binding protein adipocyte protein-2 hormone-sensitive lipase ↑carnitine ↑palmitoyl transferase-1α ↑HSL and CPT-1α genes ↓PPAR-γ and aP2	91
Berberine	Solid lipid nanoparticles (SLNs)	Diabetes	db/db diabetic mice	100 mg/kg	76.8 nm	↓Body weight, fasting blood glucose levels, HOMA-IR ↑impaired glucose tolerance	98
	O-hexadecyl-dextran	High glucose stress induced apoptosis in hepatocytes	Primary hepatocytes cells derived from the liver of Sprague-Dawley rats	0.125 mg to 2.0 mg	238±18 nm	↓ROS ↓Caspase activation ↓Oxidative stress	99
PLGA-PEG-PLGA block copolymers	High LDL cholesterol	Hep-G2 cells		42–63 nm	Modulation of PCSK-9 mRNA	100
Naringenin	Alginate-coated chitosan core-shell	Diabetes	STZ-diabetic rats		150–300 nm	No toxicity, better therapeutic effect	128
Quercetin	(QUE/P) NP	Diabetic nephropathy	Diabetic rats	10 mg/kg	32 nm	Downregulation of ICAM-1 expression	113
	pH sensitive chitosan-alginate core-shell	Diabetes	Human colonic epithelial cell line HT29 and STZ-induced diabetic rats	100 mg/kg	91.58 nm	↓Serum AST, ALT and ALP levels	114
	PLGA NPs	Diabetes	STZ-induced diabetic rats	150 mg/kg	179.9±11.2 nm	↑CAT and SOD levels ↓Drug doses	116
	Nanoemulsion	Oxaliplatin-induced neuro- and hepatotoxicity	BALB/c mice	20 mg/kg		↓Inflammation, pain, and apoptosis exploited by oxaliplatin and prevented oxaliplatin-induced neuro- and hepatotoxicity	115
Quercetin nanorods	Diabetes	Alloxan-induced diabetic rats	20 mg/kg body weight	15.4 nm	↓FBG level in blood ↓G6Pase and FBPase ↓SOD, CAT, GSH, and –SH ↓AST, ALP, and ALT	117
Emodin	PEGMA-DMAEMA-MAMMAM nanomacromolecule	Diabetic neuropathic pain	T2DM induced by HFdiet with low dose of STZ injection in rats	1 mg/mL per rat		↓Upregulation of TNF-α protein, P2X3 receptor, and the phosphorylation of ERK1/2 in the DRG of T2DM	120
Nano emodin transferosome	Antiobesity	HF-diet-induced obesity in rats		292.2 nm	Upregulation of ATGL protein expression, downregulation of G0S2 protein expression, body weight, and adipocyte size	121
Gymnemic acid	Nanosuspension	Diabetes	Diabetes-induced rats			↓Blood glucose levels	124
Baicalin	Nanostructured lipid carriers	Diabetes	STZ-induced diabetic rats		92±3.1 nm	↓FBS, HbA1c, and TG levels	128
Scutellarin	Amphiphilic chitosan derivatives (Chit-DC-VB12)	Diabetic retinopathy	Caco-2 cells and STZ-induced diabetic rats		150–250 nm	Downregulation of expression of VEGFR2, VEGF, and vWF	132
Resveratrol	Nanoliposomes	Diabetes mellitus	STZ-induced diabetic cells	30 µg/mL of resveratrol	215 nm	↑ROS-inactivating enzymes including GSH-Px and SOD	143
Nanocapsule	Blood pressure regulation	HF-diet- induced diabetic mice		207 nm	Regulation of systolic and diastolic blood pressure	144
Silybin	PLGA polymers	Systemic hyperglycemia	STZ-induced diabetic rats			↑Antioxidant characteristics, regenerative impacts on beta cells' membrane permeability	149
Myricitrin	SLNs	Diabetes	Hyperglycemic myotube cells and STZ-nicotinamide- induced T2DM mouse		76.1 nm	Improvement of SOD level, ↑muscle and myotube glycogen content, Glut4 gene expression in skeletal muscle and C2C12 cells, Bcl-2 gene expression, Bax to Bcl-2 ratio of myotubes	153
Stevioside	Pluronic-F-68 copolymer-based PLA nanoparticles	Diabetes	In vitro release study	10 mg NPs	110–130 nm	↑Intestinal absorption, bioavailability ↑Biocompatibility controlled release	156
α-eleostearic	Bitter Gourd Seed Oil Nanoemulsion	Diabetes mellitus	Alloxan-induced diabetic rats	0.5% and 1%	<100 nm	↑PPAR-γ ↑GPx, SOD, and CAT	158

Abbreviations: PBLG-PEG-PBLG, poly (gamma-benzyl l-glutamate)-poly (ethylene glycol)-poly (gammabenzyl l-glutamate); H₂S, hydrogen sulfide; CNPs @GMs, curcumin nanoparticles@ gelatin microspheres; STZ, streptozotocin; SNEDDS, self-emulsifying drug delivery system; PLGA-PVA, Poly (lactic-co-glycolic acid)-Polyvinyl alcohol; HDL, high-density lipoprotein; SGCs, satellite glial cells; DRG, dorsal root ganglia; HSL, hormone-sensitive lipase; HOMA-IR, homeostasis assessment of insulin resistance; LDL, low-density lipoprotein; QUE/P, Que/poly (ethylene glycol)-block-(poly(ethylenediamine l-glutamate)-graft-poly(ε-benzyloxycarbonyl-l-lysine)) (PEG-b-(PELG-g-PZLL)); FBG, fasting blood glucose; TG, triglycerides.