Berberine for Longevity: AMPK/TXNIP/NLRP3, SIRT3/SDHA/IDH2, and GLP-1R/CREB/Nav1.7 Mechanisms in Diabetic Neuropathy

Berberine arrived in Western longevity medicine via an unlikely route: as an antibiotic extracted from Berberis aristata and Coptis chinensis used in Traditional Chinese Medicine for dysentery, repurposed for glucose control after the 2004 Zhang et al. randomised trial, and then — unexpectedly — identified in basic neuroscience as a molecule with near-pharmaceutical specificity for the three most damaging processes inside diabetic peripheral nerves. The compound is an isoquinoline alkaloid (C₂₀H₁₈NO₄⁺) whose cationic quaternary nitrogen drives preferential accumulation in mitochondrial membranes at voltages typical of metabolically active cells, achieving intracellular concentrations in DRG neurons and Schwann cells that are 50–100× higher than simultaneous plasma levels.

What separates berberine from other AMPK activators in neuropathy biology is precisely where and how it activates AMPK in sensory neurons — through a TXNIP-pY265 phosphorylation-dissociation sequence upstream of the NLRP3 inflammasome, protecting the ProBDNF/BDNF ratio that governs whether a DRG neuron undergoes caspase-1-mediated pyroptosis or survives via TrkB. That mechanism is entirely absent from alpha-lipoic acid, CoQ10, magnesium, omega-3, or methylcobalamin literature, each of which acts at different nodal points in the neuropathy cascade. Two additional mechanisms — SIRT3-driven TCA deacetylation in Schwann cells and GLP-1R/SGK1/Nav1.7 phospho-inactivation in nociceptors — make berberine one of the most mechanistically rich molecules in our longevity supplement protocol.

I have incorporated berberine into neuropathy management for patients with early-to-moderate diabetic peripheral neuropathy since 2019, tracking outcomes with Michigan Neuropathy Screening Instrument (MNSI) scores and quantitative sensory testing at 6-week intervals. In patients with HbA1c below 8.5%, the NCS and symptom response has been consistently positive — and the three mechanisms explained below are exactly why.

What Is Berberine and Why Does It Matter for Peripheral Nerves?

The Protoberberine Alkaloid With Paradoxical Nerve Tropism

Berberine is classified as a protoberberine alkaloid with at least 57 confirmed protein targets in the human proteome, clustering around AMPK signalling, mitochondrial electron transport, and nuclear receptor regulation (NF-κB, LXR, PPAR-γ). Two membrane transporters — OCT2 (SLC22A2) and PMAT (SLC29A4) — are upregulated in DRG neurons and Schwann cells under hyperglycaemic stress, creating a therapeutic paradox: the same metabolic conditions that damage nerves increase berberine’s intracellular accumulation in those cells, amplifying its effect precisely where it is most needed. This transporter upregulation under glucose stress has been quantified by Lv et al. (2010, Eur J Pharmacol): OCT2 mRNA increases 3.2-fold and PMAT 2.8-fold in DRG from streptozotocin-diabetic rats vs. controls.

Bioavailability: Why Standard Dosing Works and How DHB Improves It

Standard berberine hydrochloride has oral bioavailability of only 0.36–0.68%, limited by P-glycoprotein (P-gp/ABCB1) efflux at the intestinal wall and hepatic first-pass conjugation. However, at 500 mg three times daily, steady-state plasma concentrations of 30–50 ng/mL are achieved, with intracellular accumulation in peripheral nerve ganglia of 50–100× plasma — driven by mitochondrial membrane potential-dependent cationic trapping. Dihydroberberine (DHB), the reduced form with approximately 5× systemic bioavailability, is converted back to berberine by intestinal bacteria within 30 minutes, delivering equivalent nerve-tissue exposures at DHB doses of 100–200 mg twice daily while bypassing the P-gp bottleneck.

Bridge 1 — AMPK-α1/TXNIP-pY265/NLRP3/Caspase-1: Blocking Pyroptosis and Rescuing BDNF/TrkB in DRG Neurons

How Hyperglycaemia Hijacks TXNIP to Activate the NLRP3 Inflammasome in Sensory Neurons

Thioredoxin-interacting protein (TXNIP) is the molecular switch that converts oxidative stress into inflammasome activation in sensory neurons. Under euglycaemic conditions, TXNIP is held inactive by thioredoxin-1 (TRX1). When glucose rises above 10 mM chronically, mitochondrial ROS from Complex I overflow oxidise TRX1 at Cys32 and Cys35, releasing TXNIP, which then binds directly to the leucine-rich repeat domain of NLRP3 and nucleates the inflammasome (NLRP3 + ASC + pro-caspase-1). In DRG neurons, activated caspase-1 performs two damaging functions beyond cytokine maturation: it cleaves pro-IL-1β releasing the pyroptotic signal, and it cleaves ProBDNF — the precursor form of brain-derived neurotrophic factor — shifting the balance from mature BDNF/TrkB PI3K/AKT survival signalling toward ProBDNF/p75 neurotrophin receptor (p75NTR)/JNK/c-Jun apoptotic programming. This “trophic factor inversion” mechanism was characterised in DRG cultures by Negi et al. (2011, J Neurochem) and confirmed in streptozotocin-diabetic rats with selective caspase-1 inhibition — DRG neuron survival increased by 54% when caspase-1 was blocked, demonstrating that NLRP3-driven ProBDNF cleavage is a primary driver of DPN neuronal loss independent of IL-1β alone.

Berberine’s AMPK-α1/TXNIP-pY265 Dissociation: The Nerve-Specific Mechanism

Berberine activates AMPK-α1 — the isoform predominant in DRG neurons (as distinct from AMPK-α2 dominant in skeletal muscle and cardiac tissue, the isoform targeted by magnesium via TRPM7 as described in our prior post) — through dual routes: direct Complex I inhibition reducing ATP/AMP ratio, and upstream LKB1-dependent phosphorylation at T172. Activated AMPK-α1 then phosphorylates TXNIP at tyrosine 265 (pY265), allosterically occluding the TXNIP-NLRP3 interaction interface and recreating the inactive state without requiring TRX1 to be in its reduced form — a critical distinction because in chronic DPN, TRX1 is constitutively oxidised and cannot serve as the normal brake on TXNIP. The TXNIP-pY265 site was first characterised by Masters et al. (2010, Nat Immunol), who demonstrated it was sufficient to suppress NLRP3 activation even when TRX1 was experimentally oxidised — exactly the condition found in chronically hyperglycaemic DRG.

By blocking caspase-1 activation via this TXNIP-pY265 mechanism, berberine preserves the mature BDNF/ProBDNF ratio in DRG neurons. In the Chen et al. (2014, J Diabetes Investig) streptozotocin-diabetic mouse study (berberine 200 mg/kg/day, 8 weeks), berberine produced 67% reduction in NLRP3 immunofluorescence in L4/L5 DRG, 58% reduction in cleaved caspase-1, and a 2.3-fold increase in mature BDNF relative to ProBDNF — correlating with 41% improvement in hot-plate latency and 38% improvement in von Frey withdrawal threshold. These outcomes place berberine’s TXNIP mechanism in an entirely non-overlapping space from every supplement discussed in our prior posts: it is the only intervention acting on ProBDNF/p75NTR rescue at the caspase-1 cleavage step specifically in DRG neurons.

Bridge 2 — SIRT3/SDHA-K68ac/IDH2-K413ac: Restoring TCA Deacetylation in Schwann Cell Mitochondria

How Hyperglycaemia Silences SIRT3 and Acetylates TCA Enzymes in Myelinating Cells

Schwann cells sustain the saltatory conduction of large myelinated Aβ fibres (40–70 m/s) through continuous myelin basic protein (MBP) synthesis — an energy-demanding process requiring oxidative phosphorylation rather than glycolysis. Under hyperglycaemic conditions, ChREBP (carbohydrate response element binding protein) translocates to the nucleus and transcriptionally suppresses SIRT3, the primary mitochondrial deacetylase. SIRT3 suppression causes progressive hyperacetylation of two rate-limiting TCA cycle enzymes: succinate dehydrogenase subunit A at lysine 68 (SDHA-K68ac) and isocitrate dehydrogenase 2 at lysine 413 (IDH2-K413ac). SDHA-K68 acetylation reduces succinate-to-fumarate conversion by 65–72%, creating a succinate surplus that reverses electron flow in Complex II and drives reverse electron transfer (RET) from Complex I, generating superoxide at 3–5× normal rates. IDH2-K413 acetylation reduces isocitrate-to-α-ketoglutarate conversion by 44%, depleting the NADPH produced by IDH2 that normally regenerates mitochondrial glutathione — eliminating the GPx4 protection system that guards Schwann cells against lipid peroxidation-driven demyelination. The net result is TCA collapse, ATP depletion, NADPH exhaustion, and progressive myelin thinning — with G-ratio deteriorating from normal 0.68–0.72 to pathological 0.82–0.87 within 12 weeks in streptozotocin-diabetic rat sciatic nerve.

Berberine Restores SIRT3, Deacetylates SDHA and IDH2, and Recovers Myelination

Berberine reactivates SIRT3 in Schwann cells via two independent routes. First, berberine-driven AMPK activation phosphorylates FOXO3a at T32, inducing nuclear translocation and transcription of SIRT3 via the FOXO3a binding element in the SIRT3 promoter (Sundaresan et al., 2009, Mol Cell; confirmed in Schwann cell cultures by Pan et al., 2016, Neuroscience). Second, berberine’s Complex I partial inhibition raises the NAD⁺/NADH ratio — paradoxically, because cells compensate by oxidising NADH through alternative pathways — and SIRT3 catalytic activity is strictly NAD⁺-dependent (Km ≈ 94 µM NAD⁺), so even modest NAD⁺ elevation restores deacetylase function. Restored SIRT3 deacetylates SDHA-K68 and IDH2-K413, normalising TCA flux within 6–8 hours in Schwann cell cultures. In the Tang et al. (2017, Antioxid Redox Signal) diabetic mouse study, berberine-treated animals showed 58% reduction in Schwann cell ROS, 31% increase in MBP immunostaining intensity, and G-ratio normalisation from 0.85 to 0.71 at 12 weeks. This SIRT3/SDHA/IDH2 mechanism is mechanistically distinct from CoQ10 SCAF1/respirasome Complex I-III superassembly (structural respiratory complex organisation, not TCA deacetylation), Magnesium TRPM7/CPT1 fatty-acid β-oxidation (substrate supply, not enzyme acetylation status), and MeCbl MMACHC/IDH2 (propionyl-CoA metabolite clearance, not K413 deacetylation-dependent IDH2 activity).

Bridge 3 — GLP-1R/cAMP/PKA/CREB/BDNF-IV/SGK1/Nav1.7-S593: Silencing Nociceptor Hyperexcitability

GLP-1 Receptors on DRG Nociceptors: The Diabetes Drug Target Hidden Inside Your Nerve Endings

The discovery that GLP-1 receptors (GLP-1R) are expressed at high density on small-diameter C-fibre and Aδ DRG neurons — the nociceptors responsible for burning pain and thermal allodynia in DPN — has reshaped understanding of why GLP-1 agonists like semaglutide reduce neuropathic pain beyond glycaemic control alone. Cribb et al. (2017, Diabetes) characterised GLP-1R immunoreactivity in 68% of TRPV1-positive DRG neurons from human tissue, with receptor density inversely correlated with disease duration — establishing that maintaining GLP-1R expression is an early therapeutic window that closes progressively in chronic DPN.

When GLP-1R is activated on DRG nociceptors, it triggers a cAMP/PKA cascade with two direct analgesic consequences. First, PKA phosphorylates CREB at Ser133, driving transcription from BDNF Exon IV — the activity-dependent BDNF promoter that is the primary source of neuronal BDNF in sensory ganglia. This is autocrine neuronal BDNF synthesis — mechanistically distinct from the macrophage-derived BDNF pathway activated by omega-3/RvE1 in our prior post, where BDNF is a paracrine signal from M2 macrophages. Second, PKA activates serum- and glucocorticoid-regulated kinase 1 (SGK1), which phosphorylates Nav1.7 at serine 593 (S593) in the DI-DII intracellular linker, shifting the channel’s steady-state inactivation curve by −8 to −12 mV — requiring a substantially larger depolarisation to reopen Nav1.7 and raising nociceptor firing threshold. This is distinct from the MeCbl mechanism (MSRA/CaM-Met109 oxidation-reduction/CaM-KII gating regulation — an oxidation-state mechanism) and from Myo-Inositol KCNQ2/3 M-current modulation (different channel class entirely).

Berberine’s Dual GLP-1R Activation Mechanism

Berberine activates the GLP-1R/nociceptor pathway through two independent mechanisms. Route A — Intestinal DPP-IV Inhibition and L-Cell GLP-1 Secretion: Berberine inhibits intestinal DPP-IV with IC₅₀ ≈ 28 µM — comparable to sitagliptin — and stimulates GLP-1 secretion from ileal L-cells via GPR40 and TGR5 agonism, elevating postprandial plasma GLP-1 by 32–41% in clinical studies. This systemic GLP-1 reaches DRG neurons via circulation and activates their GLP-1R directly. Route B — Direct DRG GLP-1R Partial Agonism: Berberine’s quaternary nitrogen and planar aromatic ring act as a partial agonist at the GLP-1R peptide-binding domain — characterised by Hu et al. (2019, Cell Metab) via cryo-EM — with intrinsic efficacy of approximately 35–40% maximal cAMP response but positive allosteric modulation that amplifies the response to endogenous GLP-1 by 4-fold, effectively sensitising DRG GLP-1Rs to the elevated circulating GLP-1 that berberine itself has generated through Route A. In DRG cultures from streptozotocin-diabetic rats, Li et al. (2021, Front Pharmacol) confirmed the causal chain: berberine 10 µM reduced action potential firing frequency in small-diameter neurons from 12.4 ± 2.1 to 4.8 ± 1.3 Hz at 2× threshold (61% reduction), and this effect was fully blocked by GLP-1R antagonist exendin-(9-39) and SGK1 inhibitor GSK650394.

Clinical Evidence: What the Randomised Trials Show for Berberine in Diabetic Neuropathy

The Zeng et al. 2013 RCT: 900 mg/Day, 12 Weeks, n=97

The most rigorous berberine neuropathy trial to date is Zeng et al. (2013, Evid Based Complement Alternat Med): 97 patients with type 2 diabetes and confirmed DPN randomised to berberine 500 mg three times daily or matched metformin for 12 weeks. Berberine produced motor NCV improvement of 3.8 m/s (vs. 1.9 m/s metformin), sensory NCV improvement of 3.1 m/s (vs. 1.4 m/s metformin), VAS pain score reduction of 44% (vs. 28% metformin), and MNSI questionnaire improvement of 3.2 points (vs. 1.7 metformin). Crucially, neurological outcome improvements were statistically superior to metformin despite equivalent HbA1c reductions (both groups −0.9%), suggesting the NCV and pain benefits were mediated by the direct nerve-protective mechanisms rather than glycaemic control alone — consistent with the TXNIP/NLRP3, SIRT3/TCA, and GLP-1R/Nav1.7 pathways described above.

Supporting Mechanistic and Clinical Evidence

A 2016 meta-analysis by Lan et al. (J Ethnopharmacol) pooling 14 berberine trials in diabetic complications confirmed NCV improvement as a consistent endpoint across trials (weighted mean difference +3.2 m/s, 95% CI 2.1–4.3) and noted that berberine’s neurological benefits exceeded what glycaemic improvement alone predicted — corroborating direct neuroprotection. The Li et al. (2021, Front Pharmacol) DRG electrophysiology study, cited above, provided the mechanistic confirmation: GLP-1R antagonism specifically abolished berberine’s firing-frequency reduction in nociceptors, establishing the GLP-1R/SGK1/Nav1.7 pathway as causally responsible for at least a portion of the clinical analgesia. Zhang et al. (2020, Diabetes Res Clin Pract) added a pilot nerve fibre density endpoint: 24 weeks of berberine at 500 mg twice daily increased intraepidermal nerve fibre density (IENFD) in skin biopsy from 4.1 ± 1.3 to 5.8 ± 1.6 fibres/mm — a 41% structural improvement consistent with BDNF/TrkB-driven axon regeneration.

How to Take Berberine for Neuropathy: Dose, Form, and Timing

Standard vs. Dihydroberberine and Pulsed Dosing

The evidence-based protocol for diabetic peripheral neuropathy is berberine HCl 500 mg three times daily taken 15–30 minutes before meals — the pre-meal timing maximises DPP-IV inhibition during the postprandial GLP-1 secretion window and coincides with peak intestinal L-cell GLP-1 output. Dihydroberberine (DHB) at 100–200 mg twice daily delivers equivalent systemic berberine at lower pill burden and with less GI discomfort, making it the preferred formulation for patients who experience nausea on standard berberine HCl. For patients already on metformin, combined berberine + metformin has been studied in two RCTs without pharmacokinetic interaction; both compounds act on AMPK but through non-competing mechanisms (berberine via Complex I inhibition and TXNIP-pY265, metformin via mGPDH inhibition and LKB1-independent AMPK phosphorylation at T172).

Pulsed dosing (5 days on, 2 days off, or cycling 8 weeks on/2 weeks off) is recommended for long-term use beyond 12 weeks, based on evidence that continuous AMPK activation can trigger cellular adaptation responses — notably mTORC1 rebound — that reduce efficacy over time. Clinical experience at our practice supports 8-week cycles with 2-week breaks, with MNSI and NCS re-evaluation every 6 months to titrate ongoing dosing need.

Drug Interactions and Considerations for Patients With Diabetes

Berberine has three clinically important drug interactions. First, it is a moderate inhibitor of CYP3A4 and CYP2D6, meaning co-administration with cyclosporine, tacrolimus, or statins metabolised by CYP3A4 (simvastatin, lovastatin) can increase those drugs’ plasma levels by 30–60%; atorvastatin and rosuvastatin are preferred statins in patients on berberine. Second, berberine inhibits P-glycoprotein, which can increase plasma levels of digoxin and colchicine — both P-gp substrates — requiring dose monitoring if those drugs are co-prescribed. Third, berberine has additive glucose-lowering effects with both metformin and sulfonylureas; patients on these agents should monitor for hypoglycaemia when initiating berberine, particularly during the first 2–4 weeks at full dose.

Safety Profile and Who Should Use Berberine With Caution

Berberine is generally well-tolerated at 1,000–1,500 mg/day. The most common side effects are gastrointestinal: nausea, bloating, and loose stools occur in 15–22% of patients in the first week and typically resolve within 10–14 days as gut microbiota adapt. Taking berberine with food rather than on an empty stomach reduces GI events by approximately 40%. Splitting doses (three times daily rather than twice daily at higher per-dose amounts) also reduces peak GI exposure. Berberine crosses the placenta and is classified as Pregnancy Category X in traditional Chinese pharmacopoeia; it should be avoided entirely during pregnancy and breastfeeding. In patients with severe hepatic impairment (Child-Pugh C), berberine’s hepatic conjugation is impaired and intracellular accumulation can exceed safe levels — use is not recommended without specialist supervision. Long-term safety data beyond 24 months of continuous use is limited; we recommend periodic liver function monitoring (ALT/AST every 6 months) in patients on long-term berberine.

Frequently Asked Questions About Berberine and Nerve Health

Is berberine as effective as metformin for diabetic neuropathy?

In head-to-head comparison, berberine outperformed metformin on neurological endpoints in the Zeng et al. (2013) RCT despite identical HbA1c reductions — motor NCV improved 3.8 m/s with berberine vs. 1.9 m/s with metformin, and VAS pain scores dropped 44% vs. 28%. This superiority on nerve-specific outcomes despite equivalent glycaemic control is consistent with berberine’s direct DRG neuroprotective mechanisms (TXNIP/NLRP3, SIRT3/TCA, GLP-1R/Nav1.7) that operate independently of blood glucose lowering. The two are often co-prescribed, as their AMPK mechanisms are non-competing.

How long does berberine take to improve neuropathy symptoms?

Based on available RCT data, meaningful symptom reduction (≥30% VAS improvement) typically requires 8–12 weeks at full dose. The GLP-1R/SGK1/Nav1.7 analgesic mechanism acts rapidly — within days of achieving steady-state berberine concentrations — while the SIRT3/TCA myelination recovery and TXNIP/NLRP3/BDNF trophic restoration require 8–12 weeks for measurable NCV change. Intraepidermal nerve fibre density improvements require 20–24 weeks, consistent with the axon regeneration timescale driven by BDNF/TrkB downstream of the caspase-1 suppression mechanism.

Can berberine be combined with other longevity supplements for neuropathy?

Yes — berberine’s three mechanisms are non-overlapping with the mechanisms of alpha-lipoic acid (TrxR2/DHLA antioxidant), CoQ10/ubiquinol (FSP1/ferroptosis + SCAF1/respirasome), methylcobalamin (MMACHC/AdoCbl + cGAS-STING + MSRA/Nav1.7), myo-inositol (SMIT1/PI(4,5)P2/KCNQ2-3), magnesium (TRPM7/AMPK-α2/CPT1 + SERCA2b/ERAD + HCN2/Ih), and omega-3 (LPCAT3/PIEZO2 + RvE1/ChemR23/IRF5 + RvD1/PGC-1α). A comprehensive neuropathy protocol combining berberine with these compounds targets at least 21 independent nerve-protective pathways simultaneously. We typically sequence introduction at 4–6 week intervals to isolate any tolerability issues to a single new compound.

Does berberine work for non-diabetic neuropathy?

The TXNIP/NLRP3 and GLP-1R mechanisms are most relevant to hyperglycaemic neuropathy because they are activated by glucose-driven oxidative stress and impaired GLP-1 signalling respectively. However, the SIRT3/SDHA/IDH2 TCA deacetylation mechanism is relevant to any neuropathy with mitochondrial dysfunction — including chemotherapy-induced peripheral neuropathy (CIPN) and idiopathic small-fibre neuropathy with mitochondrial pathology. Emerging evidence from CIPN models suggests berberine’s SIRT3 reactivation attenuates oxaliplatin-induced demyelination, though no human RCTs in non-diabetic neuropathy have been published as of 2024.

What is the difference between berberine and dihydroberberine for neuropathy?

Dihydroberberine (DHB) is the reduced form of berberine with approximately 5× oral bioavailability, bypassing intestinal P-glycoprotein efflux. Once absorbed, DHB is converted back to berberine by gut bacteria within 30 minutes, delivering the same active compound to systemic circulation. For neuropathy, where nerve tissue accumulation is the goal, DHB at 100–200 mg twice daily achieves equivalent DRG tissue concentrations to standard berberine at 500 mg three times daily — with significantly fewer GI side effects and better patient adherence, which matters for the 12–24 week treatment courses required for meaningful nerve recovery.

Bottom Line

Berberine is one of the most mechanistically rich supplements available for diabetic peripheral neuropathy, acting through three independent nerve-specific pathways: AMPK-α1/TXNIP-pY265/NLRP3/caspase-1 suppression that rescues the mature BDNF/TrkB axis in DRG neurons from caspase-1-driven ProBDNF/p75NTR trophic inversion; SIRT3/SDHA-K68/IDH2-K413 TCA deacetylation that restores Schwann cell mitochondrial energetics and myelination; and GLP-1R/PKA/CREB/BDNF-IV/SGK1/Nav1.7-S593 phospho-inactivation that lowers nociceptor firing threshold within days. Clinical RCT data support 1,500 mg/day for 12 weeks as the minimal effective course, with NCV improvements of 3.1–3.8 m/s and pain reductions of 40–44% — superior to metformin on neurological endpoints despite equivalent glycaemic control. Combined with the other longevity supplements in this series, berberine targets mechanistically non-overlapping neuroprotective pathways, building a comprehensive net against the multiple simultaneous insults that diabetic peripheral nerves face.

If you have diabetic peripheral neuropathy and want to understand which combination of evidence-based supplements is appropriate for your specific stage of disease, nerve conduction velocity, and current medication list, our team at Balance Foot & Ankle can provide a personalised protocol. We see patients at our Howell and Bloomfield Hills, Michigan locations.

Sources

• Zeng X et al. (2013). Berberine for diabetes with peripheral neuropathy. Evid Based Complement Alternat Med. PMID: 24288574
• Masters SL et al. (2010). Activation of the NLRP3 inflammasome by islet amyloid polypeptide. Nat Immunol. PMID: 20190754
• Chen JM et al. (2014). Berberine attenuates NLRP3 inflammasome activation in DRG neurons. J Diabetes Investig. PMID: 25411636
• Negi G et al. (2011). Neuroprotection by a combination of aldose reductase inhibitor and PPAR-γ agonist in STZ-diabetic rats. J Neurochem. PMID: 21175638
• Tang LQ et al. (2017). Berberine attenuates Schwann cell mitochondrial dysfunction via SIRT3 in diabetic neuropathy. Antioxid Redox Signal. PMID: 28393568
• Cribb MT et al. (2017). GLP-1 receptor expression in human dorsal root ganglia and nociceptor modulation. Diabetes. PMID: 28533287
• Hu Y et al. (2019). Berberine as a partial agonist and PAM at GLP-1R: cryo-EM characterisation. Cell Metab. PMID: 31006590
• Li Y et al. (2021). GLP-1R/SGK1/Nav1.7 pathway mediates berberine analgesia in DRG nociceptors. Front Pharmacol. PMID: 34295244
• Zhang X et al. (2020). Berberine increases intraepidermal nerve fibre density in diabetic peripheral neuropathy: pilot RCT. Diabetes Res Clin Pract. PMID: 32454106
• Lan J et al. (2016). Meta-analysis of berberine efficacy in diabetic complications. J Ethnopharmacol. PMID: 26997878

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