Circulat®

The solution for circulatory problems.
Doctor and Patient

Circulat® is a major breakthrough as an aid for restoring vascular health.

For Health Professionals & Physicians

Scientific Rationale

Surrogate laboratory endpoints of dysglycemia have been the targets for “treatment” of Diabetes Mellitus for almost a century, and there have been many pharmaceutical agents developed to reduce FBG and HbA1c. But the development of agents targeting the underlying pathologies of micro- and macro-vascular complications in these patients has had considerably less success. Unfortunately, many clinical trials have failed to show healing of diabetic foot ulcers often leading to amputation, or to reverse ischemic defects of the myocardium often heralding myocardial ischemia in many patients with diabetes. Careful protection of feet with stimulation of fibroblasts and/or major improvements in life-style (diet/exercise) with reduced platelet aggregation have not met the challenges of DFU and MI. Healing of ischemic tissues in the lower extremities or the myocardium is multi-factorial, biologically complex and clinically challenging. The pictorial representation below emphasizes the importance of vascular blood flow, a view perhaps oversimplified in clinical therapy programs in the past.

Scientific rationale and the importance of vascular blood flow

Circulat® — a multicomponent botanical product — has been designed to increase arterial flow into tissues, which are then also metabolically and immunologically better able to respond and to restore integrity and strength. Circulat® contains well-characterized and well-known “actives”, predominantly hydro-alcoholic plant extracts, that target biological mechanisms important in increasing blood flow to healthy tissue and in reversing pathologies of ischemia. Circulat® has reliable research results on the synergistic mechanisms for the medicinal plant extracts in the product formulation. It shows impressive clinical results in large numbers of patients with Diabetes Mellitus. The information of clinical trials about use of this botanical mixture of substances to improve arterial flow and tissue response; also here are provide an overview of the clinical experience to date focusing on the efficacy of Circulat® in the treatment of DFUs.

Circulat® capsules combine botanical ingredients which are traditionally described in Complementary and Alternative Medicine.

The activities are described here in four groups which address the pathologies of reduced circulation and ischemic tissues in DM. But the logic includes a multitude of synergistic pharmacologic actions which is therefore more likely to be therapeutic in the complex biology of a DFU. That tissue is at least underperfused and hypoxic, hyperglycemic and hyperlipidemic, immunologically under-responsive, over-colonized, and under-proliferative.

The four groups of pathologies and responses which are addressed by Circulat® may be referred to as: 1. Vascular, 2. Immunologic, 3. Metabolic, and 4. Healing.

  1. Vascular — Tone and Flow. Botanical actives in Circulat® dilate arterioles directly through stimulating NO/eNOS and by inhibition of ACE, and indirectly by increasing the angiogenic responses of microcirculation. Flow is further improved by reduction in blood viscosity due both to reduction of platelet aggregation and to lowering of plasma lipids. The improvements in flow are manifest in capillary beds by effects on permeability and on vessel fragility.
  2. Immune — Responsiveness. Circulat® induces appropriate responses in several immune functions:
    1. The clinical benefit of anti-inflammatory agents is generally established; hsCRP is a known marker of cardiovascular disease, including in diabetes mellitus;
    2. Further studies have shown that reduction in cytokines/interleukins such as IL-2 and IL-6, and in mitogen-stimulated endothelial responses lessen vascular pathologies;
    3. Anti-inflammatory effects are balanced with immune-modulation (e.g., NF-kappa B) for the best ongoing tissue protection against microbial colonization and to stimulate proliferative responses.
  3. Metabolic — Energy and Enzymes, Diabetes and Lipids. Certain botanicals increase oxidative capabilities, especially in a microenvironment not poisoned by hyperglycemia. Responses to Circulat® have been measured in ATP synthesis, in protein phosphylations, in dehydrogenases, and in tricarboxylic acid cycle activity. Some components also improve basic glucose metabolism in the diabetic, improving insulin sensitivity and glucose uptake. Lowering of plasma lipids may be a primary or a secondary effect of Circulat®.
  4. Healing — Stimuli and Care. Multiple biological responses are necessary for covering an ulcer. While the supply of oxygen in good capillary flow is sine qua non, a healthy tissue environment includes the right redox levels, stimulation of fibroblasts, normalized glucose metabolism and the right tissue responses of ‘scarring’ and remodeling. And the complex response can be unsuccessful if the ulcer is not protected, as known in clinical care.

It will be noted that some plants act predominantly on one of the factors that influence a healthy response and some have multiple biochemical activities. To examine molecular mechanisms underlying Circulat®’s biological activities, the effects of Circulat® treatment on gene expression levels were examined in cultured human fibroblasts. The MRC-5 cell line exposed to Circulat® and tested with Affymetrix oligonucleotide microarrays showed significant changes in 187 genes. These included four genes (IL6, HMGA1, SLC19A2 and C4A) that have been previously implicated in the development of diabetes. A large number of the identified genes are involved in energy metabolism, protein synthesis, and glucose metabolism and signaling pathways. Synergistic actions of Circulat®’s components were also revealed.

Case Studies & Publications