Effect of nutmeg on glycemic status in rat and mice: a systematic review

HASBULLAH,; FARIDAH, Didah Nur; DEWI, Fitriya Nur Annisa; INDRASTI, Dias; ANDARWULAN, Nuri

doi:10.1590/fst.130122

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Review Article • Food Sci. Technol 43 • 2023 • https://doi.org/10.1590/fst.130122 linkcopy

Effect of nutmeg on glycemic status in rat and mice: a systematic review

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Glycemic status depicts a state of individual blood glucose level. Biochemical parameters to identify glycemic status associated with diabetes mellitus include fasting or non-fasting blood glucose, HbA1c, and oral glucose tolerance. Our present work conducted a systematic review aiming to systematically summarize the in vivo experimental results of nutmeg treatments towards the glycemic status of rats and mice. The systematic review followed PRISMA guidelines. PubMed, ProQuest, Wiley Online Library, and Google Scholar were used as databases for searching articles. Twenty-one articles that met the criteria were eventually used in this systematic review. The results of the in vivo studies revealed that the intervention of nutmeg samples in rats and mice had a positive effect. This finding was present in all reviewed articles. Overall, treatment by nutmeg samples was able to attenuate fasting blood glucose, non-fasting blood glucose, and HbA1c in rats and mice, reaching up to 94.52, 60.76, and 48.86%. We also found that nutmeg samples prepared from mace and methanol had the highest effect in reducing blood glucose. Based on this systematic review, it can be concluded that nutmeg has a positive effect on improving glycemic status and reducing the risk of DM in rats and mice.

Keywords:
blood glucose; diabetes mellitus; nutmeg; Myristica; in vivo

References	Nutmeg sample	Dosage	Duration	Outcome (Compared with NC/PC/N/I)	% Differences	Effects*
(Pashapoor et al., 2020)	Petroleum ether extract from seed of M. fragrans	50; 100; and 200 mg/kg bw	21 days	FBG < NC	-55.57	+
				FBG > PC	19.19	0
				FBG > N	130.13	0
				FBG < I	-48.28	+
(Zhao et al., 2020)	Ethanolic 70% extract from seed of M. fragrans	250 mg/kg bw	4 weeks	FBG < NC	NS	+
				FBG > N	NS	0
				FBG < I	NS	+
				HbA1c < NC	NS	+
				HbA1c > N	NS	0
				OGT test: AUC < NC	NS	+
				OGT test: AUC > N	NS	0
(Kareem et al., 2009)	Aqueous extract from kernel of M. fragrans	100 mg/kg bw	30 days	FBG < NC	-3.9	+
		100 mg/kg bw	30 days	FBG > PC	23.2	0
		100 mg/kg bw + isoproterenol 85 mg/kg bw	30 days	FBG < NC	-8.8	+
		100 mg/kg bw + isoproterenol 85 mg/kg bw	30 days	FBG > PC	NS	0
(Lestari et al., 2019)	Safrole-free nutmeg dry extracts from seed of M. fragrans Houtt	5.4 mg/200 g bw	2; 4; and 6 days	FBG < NC	-40	+
				FBG < PC	NS	+
				FBG < I	NS	+
(Eo & Ie, 2020)	Ethanolic extract from M. fragrans	273.86; 547.7; and 821.58 mg/kg bw	7; 14; 21; 28; and 35 days	FBG > PC	6.59	0
				FBG < N	-4.71	+
				FBG < I	-72.67	+
		273.86 mg/kg bw + 5mg/kg bw glibenclamide	7; 14; 21; 28; and 35 days	FBG < PC	-0.34	+
				FBG < N	-20.49	+
				FBG < I	-65.17	+
(Lestari et al., 2012)	Methanol extract from seed of M. fragrans	125; 250; and 500 mg/kg bw	6 days	FBG < NC	-94.52	+
(Lestari et al., 2012)	Methanol extract from seed of M. fragrans	125; 250; and 500 mg/kg bw	6 days	FBG < PC	-4.52	+
(Somani & Singhai, 2008)	Petroleum ether extract from seed of M. fragrans	200 mg/kg bw	2 weeks	FBG < NC	NS	+
				FBG > PC	40.25	0
				FBG < I	-12.3	+
		50; 100; and 200 mg/kg bw	Administered once at the time of the test	OGT test: AUC < NC	NS	+
		50; 100; and 200 mg/kg bw	Administered once at the time of the test	OGT test: AUC = PC	NS	+
(Rajamani et al., 2005)	Kernel and mace of M. fragrans in spices mixture	10; 30; 50 mg/kg bw	30 days	FBG < NC	-16.94	+
				FBG < N	-2.56	+
				HbA1c < NC	-48.86	+
				HbA1c = N	0.4	+
(Suganthi et al., 2005)	Kernel and mace of M. fragrans in spices mixture	10; 30; 50 mg/kg bw	30 days	FBG < NC	NS	+
(Suganthi et al., 2005)	Kernel and mace of M. fragrans in spices mixture	10; 30; 50 mg/kg bw	30 days	FBG = N	NS	+
(Nasreen et al., 2020)	Water extract of ripe seeds from M. fragrans	5 g/kg bw and 5 g/kg bw + glimepiride 1 mg/kg bw)	28 days	Non-FBG < PC	NS	+
(Nasreen et al., 2020)	Water extract of ripe seeds from M. fragrans	1.5 mg/0.1 mL and 1.5 mg/0.1 mL + glimepiride (0.0004 mg/0.1 mL)	28 days	OGT test: AUC = PC	NS	+
(Vangoori et al., 2019)	Ethyl alcohol extract from mace of M. fragrans	200 and 400 mg/kg bw	10 weeks	Non-FBG < NC	-60.76	+
				Non-FBG > PC	26.27	0
				Non-FBG > N	25	0
				Non-FBG < I	-35.02	+
(Nagja et al., 2016)	Polyherbal extract (containing seed of M. fragrans)	400 mg/kg bw	7; 14; 21; and 28 days	Non-FBG < NC	-59.44	+
				Non-FBG > PC	6.14	0
				Non-FBG > N	28.52	0
				Non-FBG < I	-53.035	+
	Water-ethanol extract of seed from M. fragrans	200 mg/kg bw	Administered once at the time of the test	OGT test: AUC < NC	NS	+
	Water-ethanol extract of seed from M. fragrans	200 mg/kg bw	Administered once at the time of the test	OGT test: AUC = PC	NS	+
(Nguyen et al., 2010)	Tetrahydrofuran lignans mixture from ethanol extract of M. fragrans	200 mg/kg bw	6 weeks	Non-FBG < NC	-14.44	+
(Han et al., 2008)	Macelignan from M. fragrans Houtt	10 and 25 mg/kg bw	14 days	Non-FBG < NC	NS	+
				Non-FBG < PC	NS	+
				Non-FBG > N	NS	0
				OGT test: AUC < NC	NS	+
				OGT test: AUC < PC	NS	+
				OGT test: AUC > N	NS	0
(Peungvicha et al., 2018)	M. fragrans in herbal formulae/combined extract	0.5 and 1 g/kg	1 and 30 days	Non-FBG 2h-PPG < NC	-16.9	+
		0.5 and 1 g/kg	1 and 30 days	Non-FBG 2h-PPG < PC	-5	+
		0.5 and 1 g/kg	30 days	HbA1c < NC	-8.79	+
				HbA1c > N	151.51	0
				HbA1c < PC	-3.49	+
(Dayanand et al., 2019)	1 part of M. fragrans Houtt in herbal formulation	10; 50; and 100 mg/kg bw	28 days	Non-FBG > NC	23.65	-
(Arulmozhi et al., 2007)	Hydroalcoholic extract from rhizome of M. fragrans Houtt	50; 150; and 450 mg/kg bw	7 days	Non-FBG < NC	-41.71	+
				Non-FBG < PC (rosiglitazone)	-1.71	+
				Non-FBG < PC (glimepiride)	-25.71	+
				Non-FBG < PC (fenofibrate)	≥ -41.71	+
				Non-FBG = N	NS	+
(Chowdhury et al., 2017)	Methanol extract from seed and mace of M. fragrans Houtt	200 and 400 mg/kg bw	4 days	Non-FBG < NC	-44.78	+
(Chowdhury et al., 2017)	Methanol extract from seed and mace of M. fragrans Houtt	200 and 400 mg/kg bw	4 days	Non-FBG > PC	17.23	0
(Sailesh & Padmanabha, 2014)	Dry extract diethyl ether of M. fragrans Houtt	NS	1; 2; and 3 weeks	Non-FBG < NC	-35.82	+
				Non-FBG > N	16.76	0
				Non-FBG < I	-50.64	+
(Othman et al., 2019)	Malabaricone C from fruits of Myristica cinnamomea King	NS	8 weeks	OGT test: AUC < NC	NS	+
(Othman et al., 2019)	Malabaricone C from fruits of Myristica cinnamomea King	NS	8 weeks	OGT test: AUC > N	NS	0
(Patil et al., 2011)	Methanol extract from mace of M. fragrans	100 and 200 mg/kg bw	Administered once at the time of the test	OGT test: AUC < NC	NS	+
				OGT test: AUC > PC	NS	0
				OGT test: AUC > N	NS	0
	Methanol extract from mace of M. malabarica	100 and 200 mg/kg bw	Administered once at the time of the test	OGT test: AUC < NC	NS	+
				OGT test: AUC < PC	NS	+
				OGT test: AUC > N	NS	0

Part of nutmeg	Dosage (mg/kg bw)	Duration (day)	Glycemic parameter	Range of % Reduction *	Average of % Reduction	References
Seed	27-500	2-30	FBG	3.90-94.52	39.31	(Kareem et al., 2009; Lestari et al., 2012, 2019; Pashapoor et al., 2020)
Seed	400	7-28	Non-FBG	16.46-59.44	38.06	(Nagja et al., 2016)
Mace	200-400	70	Non-FBG	56.02-60.76	58.39	(Vangoori et al., 2019)
Kernel and mace	10-50	30	FBG	10.31-16.94	13.97	(Rajamani et al., 2005)
	200-400	4	Non-FBG	22.48-44.78	33.63	(Chowdhury et al., 2017)
	10-50	30	HbA1c	31.47-48.86	40.17	(Rajamani et al., 2005)
Rhizome	50-450	7	Non-FBG	29.03-41.71	35.37	(Arulmozhi et al., 2007)

Extraction solvent	Dosage (mg/kg bw)	Duration (day)	Glycemic parameter	Range of % Reduction *	Average of % Reduction	References
Petroleum ether	50-200	14-21	FBG	7.90-55.57	36.18	(Pashapoor et al., 2020)
Water	100	30	FBG	3.9-8.8	6.35	(Kareem et al., 2009)
Diethyl ether	NS	21	Non-FBG	24.70-35.82	28.80	(Sailesh & Padmanabha, 2014)
Hydro-alcoholic	50-450	7	Non-FBG	29.03-41.71	35.37	(Arulmozhi et al., 2007)
Ethanolic	200-400	70	Non-FBG	56.02-60.76	58.39	(Vangoori et al., 2019)
Methanol	250-500	6	FBG	87.30-94.52	90.91	(Lestari et al., 2012)
Methanol	200-400	4	Non-FBG	22.48-44.78	33.63	(Chowdhury et al., 2017)

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[1] Legend: area under curve (AUC); fasting blood glucose (FBG); glycated haemoglobin (HbA1c); initial conditions (I); non-fasting blood glucose (Non-FBG); normal control (N); negative control (NC); the value not showed (NS); oral glucose tolerance (OGT); positive control (PC); 2 hours post-prandial glucose (2h-PPG). *Effects were declared positive (+) if FBG/non-FBG/HbA1c/AUC in OGT test ≤ PC/N/I or < NC; negative (-) if FBG/non-FBG/HbA1c/AUC in OGT test ≥ NC; no effect (0) if FBG/non-FBG/HbA1c/AUC in OGT test > PC/N/I or = NC.