The Primo Vascular System (PVS) has been hypothesized as a third circulatory system different from the blood and lymphatic systems, which might represent the anatomical substratum of acupuncture meridians and nodes. Recently, there has been emerging evidence that the PVS is critically involved in stem cell trafficking, tissue regeneration, immunological regulation, and cellular communication. Also, sulfur-rich substances, both inorganic (elemental sulfur and sulfates) and organic (allicin and ajoene from Allium sativum), have well-known antioxidant, anti-inflammatory, and cytoprotective activities. Pharmacopuncture, an integrative Korean medicine therapy that directly injects herbal extracts into acupoints or intravenous channels, has been therapeutically used for chronic degenerative disorders, but its mechanistic link with PVS is undiscovered. The present review summarizes current findings on the PVS as a stem cell niche and conduit for regeneration. We focus on sulfur compound dynamics after acupuncture and pharmacopuncture activation. This paper investigates a molecular framework for sulfur-containing and herbal pharmacopuncture that improves PVS-mediated tissue healing, particularly for chronic, end-stage, and refractory illnesses. Recent investigations on rodents have shown that the physiological activation of the PVS is associated with a considerable increase in the concentrations of sulfur and calcium in cutaneous Primo nodes (the putative acupoints). PVS contains pluripotent stem cells (primo microcells and hematopoietic stem cells) that can migrate, differentiate, and perform extra-bone-marrow hematopoiesis. Pharmacopuncture, which is the injection of herbal medicines such as Allium sativum extracts, sulfur-containing formulations, and other regenerative botanicals into PVS-related acupoints and/or into veins, delivers bioactive sulfur compounds to the PVS network, thereby overcoming circulatory limitations of the traditional circulatory system. Observations from clinical settings indicate that intravenous pharmacopuncture with herbal formulas containing sulfur or antioxidants can treat chronic nephropathy, neurodegenerative diseases, and other metabolic syndromes by reducing oxidative stress, regulating activity of MMPs, and activating PVS stem cells present locally.

PVS targeted therapy with sulfur-rich and herbal pharmacopuncture is a new regeneration approach for chronic diseases. Further PVS mapping in humans, pharmacokinetic studies of pharmacopuncture drugs in the PVS, and thorough clinical trials are necessary.

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