Peripheral nerve injuries (PNIs) can lead to significant functional deficits, and while conventional treatments exist, they often do not guarantee complete recovery [1]. This has led to increased interest in complementary and alternative medicines (CAMs) and natural products for their potential in nerve regeneration [1].

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Special nutrients and phytocompounds that help support nerve tissue repair and regeneration include a variety of natural products, particularly those found in plants, herbs, and mushrooms, as well as specific vitamins and antioxidants. These compounds exert their effects through various mechanisms, such as promoting Schwann cell proliferation and migration, modulating neurotrophic factors, reducing inflammation and oxidative stress, and influencing anti-apoptotic signaling [1] [2].

Key categories and examples of these beneficial compounds are:

Phytochemicals and Herbal Extracts

• Achyranthes bidentata: Polypeptides from this plant have been shown to promote neurite outgrowth in dorsal root ganglion (DRG) neurons through ERK1/2 activation and enhance Schwann cell migration via NOX4/DUOX2-dependent reactive oxygen species (ROS) production [1]. In vivo studies also indicate it increases the density and diameter of myelinated fibers and the number of motor neurons, promoting functional recovery after peroneal nerve injury [1].
• Astragalus membranaceus: Astragaloside IV, isolated from this herb, promotes nerve regeneration by upregulating GAP-43 expression [1]. The plant extract also enhances Schwann cell migration through FGF-2 signaling and modulates neurotrophic factors like NGF, BDNF, and CNTF, as well as pro-inflammatory cytokines [1].
• Curcuma longa (Turmeric): Curcumin, its active compound, has demonstrated neuroprotective effects and promotes nerve regeneration and functional recovery in animal models of nerve crush injury [1] [2]. It stimulates the proliferation, migration, and lamellipodia of Schwann cells [1].
• Panax ginseng: Ginsenoside Rg1, a compound from ginseng, promotes Schwann cell proliferation and migration through IGF-I and FGF-2 signaling pathways [1]. It also aids peripheral nerve regeneration by facilitating the proliferation, differentiation, and migration of Schwann cells via ERK- and JNK-dependent pathways [1] [2].
• Hericium erinaceus (Lion's Mane mushroom): Aqueous extract and polysaccharides from this mushroom have shown nerve regeneration and functional recovery after peroneal nerve crush, improving the peroneal function index, withdrawal reflex latency, and axon morphology [1].
• Pycnogenol (French maritime pine bark extract): This extract, rich in procyanidins, has demonstrated significant improvements in sciatic nerve regeneration, myelination, and functional recovery in rat models of crush injury [3]. It enhances muscle regeneration, increases fiber area, and improves myelination, while also elevating nerve growth factor (NGF) levels [3]. Pycnogenol's antioxidant and anti-inflammatory properties are believed to contribute to these neuroprotective effects [3].
• Ginkgo biloba extract (EGb 761): This extract promotes peripheral nerve regeneration and neovascularization after acellular nerve allografts in rats, partly through the modulation of genes like Vegf, Sox18, Prom1, and IL-6 [1].
• Puerarin (from Pueraria lobata roots): This active component enhances the neuroregenerative effects of silicone rubber nerve chambers, leading to increases in myelinated axons, structurally mature regenerated axons, and functional recovery [1].
• Syringic acid: This plant polyphenol promotes the proliferation and migration of Schwann cells by suppressing microRNA miR-451-5p [1].
• Ursolic acid: Has been shown to induce neural regeneration after sciatic nerve injury [1].
• Quercetin: Demonstrated growth-promoting effects on peripheral nerves in rats [1] [2].
• Baicalin: A flavonoid that induces proliferation of Schwann cells through the modulation of neurotrophic factors including glial cell-derived neurotrophic factor (GDNF), BDNF, and ciliary neurotrophic factor (CTNF) [1].
• Protocatechuic acid (from Alpinia oxyphylla Miq): Promotes Schwann cell proliferation by enhancing IGF-I signaling [1].
• Aqueous extract of Codonopsis pilosula: Also promotes Schwann cell proliferation by enhancing IGF-I signaling [1].
• Cortex Mori Radicis extract: Exhibits anti-diabetic and neuroregenerative effects in diabetic neuropathy models by activating the PI3K/Akt pathway and increasing TRPC1 expression [1].
• Jiaweibugan decoction: Ameliorates diabetic peripheral neuropathy by acting through an anti-oxidative pathway via downregulating NF-κB p65 and p38 MAPK [1].

Vitamins and Antioxidants

• Lipoic Acid (Alpha-lipoic acid (ALA) and Gamma-lipoic acid (GLA)): ALA is a neuroprotective agent that promotes peripheral nerve regeneration, is anti-inflammatory, and anti-apoptotic [2]. It significantly improves sciatic function and axonal structure recovery [2]. Both ALA and GLA induce antioxidant protective actions, reduce inflammation, and promote neuroregeneration, particularly in conditions like carpal tunnel syndrome [2].
• B Vitamins (B1, B2, B3, B5, B6, B7, B12): These act as coenzymes in numerous enzymatic processes and are critical for almost every cellular function, including those in the nervous system [2]. B12, in particular, is essential for energy generation and nerve repair pathways [2].
• Ubiquinone (CoQ10): This antioxidant possesses bioenergetic and anti-inflammatory properties, protecting neurons from apoptosis [2]. It functions as an essential cofactor in oxidative phosphorylation in mitochondria, enhancing cellular energy production and oxidative protection [2]. The ubiquinol form of CoQ10 has superior bioavailability [2].
• Vitamin C: Essential for the physiological function of the nervous system and critical for a fully functioning neurological system [2].
• Melatonin: Exhibits neuroprotective effects on injured neurons, anti-inflammatory actions at the injury site, scar-reducing properties, and stimulates stem cell proliferation and axonal regeneration [2].
• N-acetylcysteine (NAC): A neuroprotective compound that helps synthesize glutathione, a powerful antioxidant and free radical scavenger, which protects cellular membranes and mitochondrial function [2].
• Acetyl-L-carnitine: Also acts as a cellular protectant against free radicals [2].

These diverse natural compounds and nutrients offer promising avenues for supporting nerve tissue repair and regeneration, often by targeting multiple pathways involved in the complex process of nerve recovery [1] [2] [3].