Table 1 Bioactive components in an herbal mixture (P05) for GERD

Oyster shell

Crassostrea gigas Thunberg shell

Calcium carbonate

Anti-acid

• Neutralization of esophageal pH by increasing plasma gastrin levels

• Inhibition of pepsin and bile acid

[73, 75, 76]

Calcium phosphate

Anti-acid

• The phosphate ions likely react with hydrochloric acid to neutralize the pH

[77, 78]

Bamboo shavings

Bambusae Caulis in Taeniam

p-Coumaric acid (p-CA)

Prevents oxidative gastric damage by:

• Attenuating the ulcer-elevated levels of malondialdehyde

• Restoring the ulcer-depleted levels of reduced glutathione and the antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase

[38, 79]

Caffeic acid

• Attenuation of gastric mucosal damage via the NO pathway

[39, 79]

Ferulic acid

• Increase in gastric pH

• Decrease in total acidity, free acidity, and lipid peroxidation

• Inhibition of gastric acid secretion by diminishing H⁺-K⁺ATPase enzyme

[40, 79]

Poncirus immature fruit

Ponciri Fructus Immaturus

Poncirin

• Attenuation of HCl/ethanol-induced gastric lesions

• Inhibition of iNOS, COX-2, TNF-α, and IL-6 expression via the down-regulation of NF-κB binding activity

[52, 53]

Hesperidin

• Improvement of the delayed gastric emptying rate

• Inhibition of H. pylori growth

[53, 55]

Neohesperidin

• Prevention of HCl/ethanol-induced gastric lesions

• Stimulation of mucus secretion

• Increase in gastric pH by decreasing in gastric secretion and gastric acid output

[53]

Naringin

• Prevention of gastric ulcer via inhibiting inflammation markers, including TNF-α, IL-6, CRP, iNOS, and caspase-3 levels

[80]

Limonene

Neutralization of the gastric acid effect by:

• Coating the stomach wall

• Protecting the mucosal lining from gastric acid exposure

• Improvement of healthy peristalsis

[74]

Scutellariae root

Scutellaria baicalensis Georgi

Baicalin

• Down-regulation of TRPV1 in DRG neurons

[42, 45]

Baicalein

• Decrease of acute ulcers via α2-adrenoreceptors, SH compounds, NO, PG, and KATP channels

• Increases in gastric mucus secretion

• Inhibition of gastric acid secretion by suppressing the histaminergic pathway and H⁺, K⁺-ATPase activity

[43]

Wogonin

• Anti-gastric inflammatory agent via arachidonic acid metabolism such as induction of prostaglandin D2 and suppression of 5S-hydroxyeicosatetraenoic acid (5S-HETE)

• Preventive induction of profuse apoptosis in the stomach

[44]

Chrysin

Anti-inflammation

• Increase of cell proliferation effect via EGF

• Reduction of cellular apoptosis by modulating caspase-3

• Reduced TNF-α, NF-κB p65 unit, interleukin-1β (IL-1β), IL-17A, interferon- gamma (IFN-γ), IL-12 and IL-6

• Inhibitory agent against PPAR-γ

• Down-regulates pro-inflammatory enzymes, such as COX-2, myeloperoxidase (MPO), iNOS, prostanoids, and phospholipase A2

• Blocks activation of NF-κB and degradation of IL-1β-stimulated IκB-α

[49, 81]

Medicated leaven

Artemisia annua

Artemisinin

• Inhibition of H. pylori growth

• Suppression of H. pylori-induced NF-κB activation

[54]

Artesunate

• Decrease in gastric acid secretion

• Inhibition of oxidative stress markers such as malondialdehyde, glutathione, and superoxide dismutase activity

• Reversing expression of pro-inflammation markers, including TNF-α, IL-1β, IL-6, NF-κB, myeloperoxidase, and COX-2

[58, 59]

Xanthium sibiricum

Xanthinin

No previous research

Xanthatin

• Expressing anti-inflammation effect via suppression of NO production, PGE2 synthesis, and 5‐lipoxygenase activity

[60, 61]

Polygonum hydropiper

Confertifolin

No previous research

Polygodial

• Prevention of gastric mucosal lesions by regulating endogenous prostaglandins, NO, sulfhydryl compounds, and vanilloid receptor

[82, 83]

(2E)-hexenal

• Inhibition of H. pylori growth

[84]

Isoquercetrin

• Prevention of eosinophilic esophagitis through a decrease in eosinophil, neutrophil, and IL-5 levels

[85]

Vigna angularis

Angularin

• Anti-inflammatory effects through mitigation of NO production

[54]

Bitter Prunus armeniaca Kernel

Amygdalin

• Inhibition of gastric ulcer via diminishing NO production and TNF-α expression

[86]

Prunasin

• Anti-inflammatory activity via attenuation of IL-6, IL-8, IL-23, HSP70 and ICAM-1 expression

[57]

Licorice root

Glycyrrhizae Radix et Rhizoma

Glycyrrhizin

• Expressing anti-inflammatory effect through inhibiting the generation of ROS by neutrophils

[57, 58]

Glycyrrhetic acid

• Inhibition of H. pylori growth

• Inhibition of inflammatory effect via attenuating pro-inflammatory markers such as iNOS, COX-2, TNF-α, IL-1β, and IL-6

[59, 87]

Liquiritin

• Anti-inflammatory effects via attenuating pro-inflammatory markers such as iNOS, COX-2, TNF-α, IL-1β, and IL-6

[87]

Formononetin

• Decrease in gastric secretion

• Increase in mucus production

[60]

Isoliquiritin

Antioxidant:

• Activation of Nrf2 pathway

Anti-inflammation:

• Suppression of NF-κB pathway

[61]