Table 2.

Effects of ginger on fibromyalgia-like symptoms.

First Author, Year [ref]	Experimental Design and Treatments	Results
In vitro study
Ha, 2012 [36]	BV-2 cells were cultured and activated with LPS (1 mg/mL) for 12 h. LPS was removed from the cells and indicated 6-shogaol (1, 5, 10 μM) was added. NMMA, an inhibitor of iNOS enzyme activity, was used as a positive control	Compared to control group, 6-shogaol groups:
		↓ iNOS expression and release of NO
		↓ microglial activation
Hosseinzadeh, 2017 [37]	C28I2 human chondrocytes pretreated with GE (5, 25 μg/mL) for 24 h, followed by incubation with IL-1β (10 ng/mL) for 24 h	Compared to vehicle group, GE groups:
		↑ anti-oxidant enzyme gene expression
		↓ reactive oxygen species
		↓ lipid peroxidation
		↓ Bax/Bcl ratio, inhibiting apoptosis
		↓ caspase-3 activity
Animal studies
Montserrat-de la Paz, 2018 [38]	Intermittent cold stress (ICS)-induced FM model	Compared to control group, GR groups:
	Female C57BL/6 J mice (n = 48, 5-week-old)	↓ mechanical and thermal allodynia
		↓ mechanical hyperalgesia
	Treatments: healthy control, ICS group, ICS + APAP (40 mg/kg/day), ICS + GR (0.5%, 1%), and ICS + GR (0.5%) + APAP (40 mg/kg/day) supplemented with standard diet for 8 weeks	↑ improved behavioral changes related to cognitive disturbances associated with pain, anxiety, and depression ↓ proinflammatory mediators such as NO, PGE2, TXB2, IL-1β in LPS-stimulated macrophages
		↑ synergism with APAP leading to further reduction in FM-like symptoms
Fajrin, 2019 [39]	Complete Freud’s Adjuvant (CFA)-induced FM-like model	Compared to control group, RGO groups:
	Male mice (n = 48, 8-week-old)	↓ hyperalgesia in a dose-dependent manner
	Treatments: sham, negative control, RGO doses at 100, 200, 400 and 600 mg/kg orally 1x/day for 7 days	↑ thermal response threshold
Abolaji, 2017 [40]	Chlorpyrifos (CPF)-induced FM-like model	Compared to the control group, 6-GRF groups:
	Female Wistar rats (n = 70, 100–125 g)	↓ H2O2 and MDA levels
		↑ catalase, SOD, GPX activity
	Treatments: control with corn oil only (2 mL/kg BW), 6-GRF (100 mg/kg BW), CPF dissolved in corn oil (5 mg/kg BW), CPF (5 mg/kg BW) and 6-GRF (50 mg/kg BW) concomitantly, CPF (5 mg/kg BW) and 6-GRF (100 mg/kg BW) concomitantly 1x/day for 35 days after CPF toxicity	↓ NO, MPO, TNF-α
		↓ caspase-3
Zhang, 2016 [41]	DSS-induced chronic colitis model	Compared to control group, GDNP group:
	Female FVB/NJ mice (n = 7, 6–8-week-old)	↑ healing in wounded intestinal epithelial monolayers
		↑ proliferation of IECs
	Groups including control with normal feeding and GDNPs 2 (300 μL of 1 mg/mL solution) by oral gavage 1x/day for 18 weeks	↓ TNF-α, IL-6, IL-1β, MPO
		↑ IL-10, IL-22

Abbreviations: APAP, paracetamol; BW, birth weight; CFA, complete Freud’s Adjuvant; CPF, chlorpyrifos; DSS, dextran sodium sulfate; FM, fibromyalgia; ICS, intermittent cold stress; IL-1β, interleukin-1β; GE, ginger extract; GPX, glutathione peroxidase, GR, ginger rhizome; GRF, gingerol-rich fraction; H₂O₂, hydrogen peroxide; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; MDA, malondialdehyde; MPO, myeloperoxidase; NO, nitric oxide; PGE₂, prostaglandin E₂; RGO, red ginger oil; SOD, superoxide dismutase; TNF-α, tumor necrosis factor-α; TXB₂, thromboxane B2; ↑ increase; ↓ decrease; ↔ no difference.