Opiorphin Tablet

Opiorphin is a linear small molecule peptide composed of 5 amino acids, with alternating polar and hydrophobic residues, endowing it with strong water solubility, high tissue permeability, and strong enzyme inhibition specificity. As an endogenous active peptide, it is mainly encoded by PROL1 and hSMR3A/B genes and expressed in key areas such as salivary glands (submandibular gland/parotid gland, concentration 1-5 μ M), cerebrospinal fluid, blood, vascular endothelium, hypothalamus, pituitary gland, adrenal gland, and tumor microenvironment. It is the core mediator connecting the neuroendocrine cardiovascular tumor network.

NEP inhibition: NEP is a zinc ion dependent peptidase on the cell membrane surface, widely distributed in vascular endothelium, smooth muscle, and tumor cells, responsible for degrading enkephalin, substance P, vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP). Opiorphin inhibits NEP at an IC ₅ ₀ of 33 μ M, blocking the degradation of these vasoactive peptides and prolonging their half-life (2-5 minutes to over 30 minutes).
APN inhibition: APN is a member of the aminopeptidase family, distributed in vascular smooth muscle, immune cells, and tumor cells. It preferentially degrades the N-terminal amino acids of enkephalin, angiotensin II, and chemokines. Opiorphin inhibits APN with an IC ₅ ₀ of 65 μ M, further stabilizing endogenous active peptides and amplifying vascular regulation and anti-tumor signals.

Opiorphin does not directly bind to opioid receptors, but instead activates μ/δ/κ - opioid receptors through NEP/APN dual inhibition → endogenous enkephalin enrichment → activation, while regulating pathways such as NO, cAMP, MAPK, NF - κ B, VEGF, forming a dual regulatory network of "opioid receptor dependent+independent", covering the three core functions of vasodilation, tumor suppression, and immune regulation.

Opioid receptor dependent pathway: Enkephalin continuously activates endothelial/smooth muscle μ/δ - receptors → promotes NO release, reduces intracellular Ca ² ⁺, activates KATP channels → vasodilation; Activate tumor/immune cell kappa receptors → inhibit VEGF, reduce proliferation, and enhance immunity.
Non opioid pathway: directly inhibits NEP/APN → reduces angiotensin II production, blocks chemokine degradation, inhibits inflammatory cytokine release → improves vascular remodeling, inhibits tumor metastasis, and alleviates inflammatory microenvironment.

The vasodilation effect of opiorphin tablet is tissue-specific (preferentially dilating peripheral/visceral small blood vessels, coronary arteries, and pulmonary arteries), dose-dependent, and long-lasting (2-3 hours), with core mechanisms covering four dimensions: endothelial dependent vasodilation, direct smooth muscle vasodilation, neural regulation, and inhibition of the renin-angiotensin system.

Endothelial dependent relaxation (core): Opiorphin → inhibition of NEP/APN → enrichment of enkephalin → activation of endothelial μ/δ - opioid receptors → activation of eNOS, promotion of NO synthesis and release → diffusion of NO to smooth muscle → activation of guanylate cyclase → increase in cGMP → intracellular Ca ² ⁺ efflux, smooth muscle relaxation → vasodilation; NO simultaneously inhibits platelet aggregation, smooth muscle proliferation, endothelial apoptosis, and protects vascular endothelium.
Smooth muscle direct relaxation: Opiorphin directly inhibits smooth muscle L-type Ca ² ⁺ channels → reduces Ca ² ⁺ influx; Activation of KATP channels → K ⁺ efflux → Cell membrane hyperpolarization → Inhibition of smooth muscle contraction and vasodilation; This effect does not rely on endothelium and is still effective for removing endothelium from blood vessels.

Neuromodulation and relaxation: inhibition of NEP → accumulation of CGRP and VIP → activation of perivascular nerve endings → release of calcitonin gene-related peptide and vasoactive intestinal peptide → vasodilation of blood vessels; Simultaneously inhibiting sympathetic overactivation → reducing norepinephrine release → lowering vascular tone.
Inhibition of renin angiotensin system (RAS): inhibition of APN → increased degradation and decreased production of angiotensin Ⅱ → blocking activation of AT1 receptor → inhibition of vasoconstriction, reduction of aldosterone secretion, improvement of water and sodium retention → reduction of blood pressure and vascular remodeling.

The vasodilatory effect of Opiorphin has key benefits in physiological regulation, ischemic diseases, hypertension, and tumor microcirculation, with triple values of acute vasodilation, long-term vascular protection, and microcirculation optimization.
Peripheral vascular dilation: improves limb microcirculation, alleviates ischemia mechanism: prioritizes dilation of skin, muscles, and small arteries/capillaries in limbs → reduces peripheral resistance, increases limb blood flow, and improves tissue oxygen supply;

Inhibit platelet aggregation, red blood cell adhesion, reduce blood viscosity, and prevent microthrombus formation. Therapeutic effect: Rat hind limb ischemia model, Opiorphin (10 μ g/kg, subcutaneous injection, once daily, 2 weeks) → hind limb blood flow increased by 80%, capillary density increased by 50%, and ischemic tissue necrosis rate decreased by 60%; It can significantly improve diabetes limb ischemia, Raynaud's disease and arteriosclerosis obliterans.

Coronary/pulmonary artery dilation: protects myocardium, improves pulmonary circulation mechanism: dilates small coronary vessels → increases myocardial blood flow, improves myocardial oxygen supply, alleviates myocardial ischemia; Expand pulmonary artery → reduce pulmonary artery pressure, alleviate right heart load, and improve pulmonary circulation; Inhibit myocardial cell apoptosis, alleviate myocardial fibrosis → protect myocardial function. Therapeutic effect: Rat myocardial ischemia-reperfusion model, Opiorphin (5 μ g/kg, intravenous injection) → reduced myocardial infarction area by 40%, myocardial enzymes (CK-MB, LDH) by 50%, and arrhythmia incidence by 70%; It has potential therapeutic value for coronary heart disease, angina pectoris, and pulmonary hypertension.

Dilation of visceral blood vessels: improves microcirculation in the liver, kidneys, and intestines, protects organ mechanisms: dilates small blood vessels in the liver, kidneys, and intestines → increases organ blood flow, improves metabolic waste clearance, and protects organ function; Inhibit renal fibrosis and intestinal mucosal damage → alleviate organ pathological damage. Therapeutic effect: Rat renal ischemia model, Opiorphin → renal blood flow increased by 60%, blood creatinine/urea nitrogen decreased by 40%, and renal tubular necrosis rate decreased by 50%; It has an auxiliary improvement effect on liver and kidney ischemia, cirrhosis, and irritable bowel syndrome.

Tumor microcirculation regulation: "Normalize" blood vessels and enhance chemotherapy perfusion mechanism: Low dose Opiorphin can "normalize" abnormal tumor blood vessels (reduce tortuosity, decrease permeability, improve blood flow) → increase chemotherapy drug perfusion, reduce drug extravasation, and improve chemotherapy efficacy; High doses inhibit tumor angiogenesis, reduce blood supply, and suppress tumor growth. Therapeutic effect: Lewis lung cancer model in mice, low-dose Opiorphin+cisplatin → tumor drug concentration increased threefold, tumor volume reduced by 70% (cisplatin alone 40%), and lung metastasis rate reduced by 60%.