ArticleAnnals of translational medicine2021
Huperzine A lowers intraocular pressure via the M3 mAChR and provides retinal neuroprotection via the M1 mAChR: a promising agent for the treatment of glaucoma.
Article in Annals of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Calcium at the Helm: Mechanisms and Therapeutic Targets in the Retinal Neurovascular Unit.Biomolecules · 2026Review
- Amine-responsive Rhodopsin-like GPCRs in ocular pathology: mechanistic associations, candidate biomarkers, and therapeutic potential.Frontiers in physiology · 2026Review
- Erratum: Huperzine A lowers intraocular pressure via the M3 mAChR and provides retinal neuroprotection via the M1 mAChR: a promising agent for the treatment of glaucoma.Annals of translational medicine · 2024Article
- The Identification of New Pharmacological Targets for the Treatment of Glaucoma: A Network Pharmacology Approach.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Inhibition of CRMP2 Phosphorylation Suppresses Microglia Activation in the Retina and Optic Nerve and Promotes Optic Nerve Regeneration After Optic Nerve Injury.Neuromolecular medicine · 2024Article
- Huperzine A ameliorates neurological deficits after spontaneous subarachnoid hemorrhage through endothelial cell pyroptosis inhibition.Acta biochimica et biophysica Sinica · 2024Article
- Drug Treatment Attenuates Retinal Ganglion Cell Death by Inhibiting Collapsin Response Mediator Protein 2 Phosphorylation in Mouse Models of Normal Tension Glaucoma.Neuromolecular medicine · 2024Article
- Immunomodulatory and Antioxidant Drugs in Glaucoma Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Nanocarriers for the Delivery of Neuroprotective Agents in the Treatment of Ocular Neurodegenerative Diseases.Pharmaceutics · 2023Review
- Intravitreal injection of Huperzine A promotes retinal ganglion cells survival and axonal regeneration after optic nerve crush.Frontiers in cellular neuroscience · 2023Article
- Article
- A Synopsis of Multitarget Potential Therapeutic Effects of Huperzine A in Diverse Pathologies-Emphasis on Alzheimer's Disease Pathogenesis.Neurochemical research · 2022Review
- Muscarinic Acetylcholine Receptors in the Retina-Therapeutic Implications.International journal of molecular sciences · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlaucoma is a neurodegenerative disease that shares similar pathological mechanisms with Alzheimer's disease (AD). Drug treatments for glaucoma increasingly rely upon both lowering of intraocular pressure (IOP) and optic nerve protection, as lowering of IOP alone has been unsatisfactory. Huperzine A (HupA) is an acetylcholinesterase inhibitor (AChEI) used for AD. This study investigated the potential of HupA as a treatment for glaucoma.
methodsThe ability of HupA to lower IOP via causing pupil constriction was assessed using New Zealand rabbits. The retinal neuroprotective effects of HupA were assessed
resultsHupA caused pupil constriction in a dose-time dependent manner which was reversed by the nonselective muscarinic acetylcholine receptor (mAChR) antagonist atropine and the selective M3 mAChR antagonist 4-DAMP. However, HupA had no effect on isolated iris muscle tension and calcium flow indicating an indirect M3 mAChR mediated effect. HupA exerted a neuroprotective effect against I/R and OGD to attenuate the retinal pathological lesion, improve retinal neuronal cell viability, reverse oxidative stress injury by increasing GSH levels and SOD activity, and decreasing MDA content and reduce the retinal neuronal apoptosis by decreasing Bax/Bcl-2 ratio and caspase-3 expression with no effect on the calcium flow tests. The effects were abolished by atropine and the selective M1 mAChR antagonist pirenzepine in OGD-induced PRNs suggesting an indirect M1 mAChR-mediated effect via inhibiting AChE activity to increase endogenous ACh level. Furthermore, HupA increased phosphorylated AKT level and decreased the levels of phosphorylated JNK, P38 MAPK and ERK via M1 mAChR antagonists indicating an involvement of activating the M1 mAChR and the downstream AKT/MAPK signaling pathway in the protective effects of HupA.
conclusionsHupA could significantly decrease IOP via activating M3 mAChR indirectly and produce retinal neuroprotective effect through M1 mAChR/AKT/MAPK by increasing endogenous ACh level. These investigations demonstrated that HupA was an effective drug in glaucoma treatment and the clinical application of HupA and other AChEIs for glaucoma patients should be further investigated.
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