Addressing GI Health Through the Bidirectional Modulation of the Gut-Brain Axis With Herbal Extracts: A Narrative Review

Abstract

Functional gastrointestinal disorders (FGIDs) refer to a group of disorders with chronic symptoms, such as abdominal pain, dysphagia, dyspepsia, diarrhea, constipation, and bloating. Among these, functional constipation significantly impacts the quality of life and is linked with comorbidities, such as anxiety and depression. The exact pathophysiology remains unclear despite the widespread occurrence. Research suggests that the gut-brain axis plays a role in FGIDs. Disruptions in the bidirectional communication between the brain and gastrointestinal (GI) tract contribute to GI symptoms and mood disturbances. The incomplete understanding of FGID pathophysiology has led to limited treatment options. Traditional treatments often focus on single symptoms and come with side effects, prompting the need for alternative approaches that address both GI and psychological components. Alternative approaches including herbal supplements offer a natural alternative to conventional medicine by promoting regularity and gut health. Abelmoschus esculentus L. or okra has a history of use in traditional medicine. Bioactive compounds such as polysaccharides and fibers found in okra offer gastroprotective benefits. Withania somnifera is a plant commonly referred to as ashwagandha. The plant root has been used for its health-promoting effects. Research supports the use of W. somnifera to help with stress and sleep. Digexin is a herbal supplement combining W. somnifera (ashwagandha) and A. esculentus (okra). It has shown promise in improving both GI regularity and mood by modulating the gut-brain axis. Clinical studies support the potential of a novel herbal supplement that aids in the management of FGIDs. This narrative review looks at FGIDs, etiologies, current treatment, and possible therapeutic supplements to aid in symptom management.

Keywords: functional constipation; functional gastrointestinal disorder; gut health; gut-brain axis; gut-brain connection.

Figure 1. Digexin's mechanisms of action

1) Digexin reduces stress and lowers cortisol. The precise mechanism is still unknown, but it has the effect of suppressing the sympathetic nervous system (SNS). 2) Digexin boosts serotonin levels, likely through stimulation of enterochromaffin (EC) cells in the gut lining. 3) Increased serotonin has the immediate effect of stimulating the enteric nervous system (ENS) through intrinsic primary afferent neurons (IPANs) and activating local peristalsis/secretions. 4) Serotonin signals through vagal extrinsic primary afferent neurons (ExPANs), which suppress the SNS and promote the peripheral nervous system (PNS). 5) PNS is highly preferred now due to suppressed SNS from decreased stress and ExPAN promotion of PNS. 6) PNS stimulates G cells to produce gastrin, which produces stomach acid, digestive juices, gastric emptying, and peristalsis. 7) The PNS tone is conducive to digestion, stimulating peristalsis, and releasing enzymes and hormones, along with other factors. 8. *Potential secondary activation of gastrin Digexin through an increase in gastrin-releasing peptide (theoretical). This figure was created by Eric Withee and Doug Kalman.