ARA-290 42 min read January 28, 2026

ARA290: Promising Research for Inflammation & Healing

## ARA-290 Targets Cardiovascular System. "Beyond having beneficial effects on LV function, LV tissue inflammation and mitochondrial health, ARA290 reduced a systemwide frailty index in rats of advanced age. Frailty is a state of being highly vulnerable to adverse health outcomes characterized by functional decline in multiple organ systems. Previous studies have shown that LV structure and function deterioration that occur with aging are more

ARA290: Promising Research for Inflammation & Healing

by Dr. Timothy J.

ARA290 Fighting Inflammatory Cell Death (Nephrotoxicity)

"The findings indicated that ARA290 significantly reduced the DNA damage parameters of comet assay and the frequency of micronuclei induced by cisplatin. Besides, ARA290 improved cisplatin-induced oxidative stress by reducing MDA/ROS levels and enhancing antioxidant enzyme levels. In addition, reduced levels of pro-inflammatory cytokines indicated that cisplatin-induced renal inflammation was mitigated upon the treatment with ARA290. Besides, ARA290 ameliorates cisplatin-induced cell injury by antagonizing apoptosis. Furthermore, the molecular findings indicated that gene and protein levels of TNFα, IL1β, IL6, Caspase-3, and Bax were significantly decreased and gene and protein levels of Bcl2 significantly increased in the ARA290 plus cisplatin group compared with the cisplatin group. These findings revealed that ARA290 as a potent chemo-preventive agent exerted a protective effect on cisplatin-induced nephrotoxicity mostly through its anti-apoptotic, anti-inflammatory, and antioxidant potentials and also suggested that ARA290 might be a new therapeutic approach for patients with acute kidney injury... ARA 290, an 11-amino acid linear nonhematopoietic peptide derived from the three-dimensional structure of helix B of the erythropoietin (EPO), interacts selectively with the innate repair receptor (IRR) that arbitrates tissue protection." (1)

ARA290 Wound Healing.

"The diabetic foot ulcer (DFU) are serious problems to diabetes and may be associated with late healing and septic manifestation, consequently result in amputation which is an extortionate incident. The innate repair receptor (IRR) is expressed by injured tissues and is activated by erythropoietin produced and released into damaged tissue. Activation of the IRR might provide benefit for diabetic wound healing. This study evaluated effect of a specific IRR agonist, ARA290, on skin wound repair. The aim of the present study was to evaluate the effect of topical application based on ARA290, in streptozotocin-induced diabetic incision wound models rats. The treatment was performed daily, until day 14 after wound induction. Wound closure was determined and the features of the repaired tissue were examined, including amount of collagen and protein content, biochemical parameters, antioxidant status and proinflammatory cytokines. The data confirmed wound healing activities via macroscopic, biochemical, immunofluorescent and molecular methods. There was meaningful acceleration in wound closure rate, decrease in the period of re-epitalization, greater amount of collagen and protein content in ARA290 treated group when compared with control group. The increase of serum insulin and HDL was divergent with blood glucose decrease and reduced lipid level. The healing effect was confirmed by reduced levels of inflammatory cytokines and lipid peroxidation and augmented antioxidants. The results propose that ARA290-arbitrated IRR activation may signify an appealing approach to treat diabetes-associated wound healing." (2)

"The wound contracting capability of experimental rats receiving ARA290 topical administration (Group III and IV) revealed widespread wound recuperation from the 7th day onward when as compared with both normal control animals (Group I) and diabetic group (Group II). The maximum rate of wound contraction have been found in 20% ARA290 treated animals (Group IV) as compared to other groups at day 14 (Fig. 2A). As a result, the 20% ARA290 handled animal’s showed better noticeable effect." (2)

"According to the results of the wound contraction study, the epithelialization period (Fig. 2B), total collagen (Fig. 2C) and total protein content (Fig. 2D) in laboratory mice in the 14 days of the experiment followed almost the same pattern. According to the findings of the study, the time of complete epithelialization in diabetic control rats (group II) was slightly longer than in normal control animals (group I). Though, animals treated with 10% and 20% ARA290 (group III and IV) presented a quicker epithelialization rate compared to the diabetic control group (group II). As shown in Fig. 2C the collagen content of diabetic control animals (Group II) was meaningfully lesser than with normal control animals (Group I). On the other hand, animals treated with 10% and 20% ARA290 (Group III and IV) revealed noticeable enhancement in collagen content compared to diabetic control rats (Group II). As shown in Fig. 2D in protein content evaluation, the diabetic control animals (Group II), was meaningfully decreased in compared to normal control group (Group I). Besides the amount of protein content was also increased in diabetic animals treated with 10% and 20% ARA290 (group III and IV) compared to diabetic control rats (group II)." (2)

ARA-290 Targets Cardiovascular System.

"Beyond having beneficial effects on LV function, LV tissue inflammation and mitochondrial health, ARA290 reduced a systemwide frailty index in rats of advanced age. Frailty is a state of being highly vulnerable to adverse health outcomes characterized by functional decline in multiple organ systems. Previous studies have shown that LV structure and function deterioration that occur with aging are more highly correlated with the frailty index employed in our study than with chronologic age. As such, we found that through evaluation of 31 health-related variables, treatment with ARA290 improved the healthspan in late life. There were similar impacts of ARA290 in body weight. ARA290 treated rats achieved an average peak body weight at an older age than those treated with saline. When expressed as percentage of maximal lifespan in saline or ARA290 treated rats, beyond 80% of the maximum lifespan ARA290 treatment conferred higher maximal body weight, and a slower late-life decline. These results suggest that that the reduction in systemic inflammation, improvement of LV systolic function and retention of late life body weight induced by ARA290 treatment are linked to its effect to attenuate frailty and preserve healthspan in rats of advanced age.

Treatment of near middle-aged rats with ARA290 attenuated the age-associated decline in cardiac systolic function that presents beyond middle age, reduced frailty and improved late life healthspan in advanced age. Potential mechanisms that underly the effects of ARA290 to reduce the age-associated deterioration of cardiac function include the impact of ARA290 on reduction of cardiac tissue inflammation, on increased resistance to oxidative stress, on preserved protein quality control and mitochondrial function in cardiac myocytes. Systemic effects of ARA290 to preserve overall healthspan in late life are manifested in its ability to attenuate late-life body weight loss in the context of ameliorating body-wide frailty." (3)

"The mitochondrial permeability transition pore (mPTP) opening thresholds (A), cardiomyocyte autophagy flux (B), and accumulation of lipofuscin (C) in left ventricular cardiomyocytes isolated from 32-month-old rats. Statistically significant interactions between treatment groups are shown ( _P_ < 0.01, * _P_ < 0.001)."

ARA290 enhanced autophagic flux

The CM autophagy flux, which in cardiac myocytes is dominated by mitochondrial protein turnover, and assessed by the presence of autophagolysosomes was significantly enhanced in ARA290 treated rats compared to those treated with saline, indicating that treatment has a positive effect to protect mitochondrial proteostasis in advanced age ( _P_ < 0.001).

Age-associated lipofuscin accumulation was reduced by ARA290 treatment

The accumulation of undegradable cellular “wear-and-tear” byproduct, lipofuscin, widely recognized to increase with aging, and reflects an impairment of protein recycling mechanisms, was reduced in ARA290 treated vs. saline treated cardiomyocytes ( _P_ < 0.001).

Collectively, the data in Figure 7 indicates that chronic treatment with ARA290 confers increased cardiomyocyte mitochondrial fitness and cellular stress resistance compared to that in age-matched 32 months old) saline treated controls." (3)

ARA-290's Broad Anti-Inflammatory Actions.

"Activation of the IRR by ARA290 commences a local multi anti-inflammatory pathways, which inhibit death signal and up-regulate survival signals and subsequently blocks inflammation-induced apoptosis, stimulates tissue restorative functions and produces nitric oxide by endothelial cells and subsequently inhibiting obvious tissue damage[24, 26, 27]. Besides, activation of the IRR also stimulates tissue repair responses, including free radical scavenging[28]. ARA 290 has been assessed widely in a broad field of preclinical studies. The findings of these reports reveal that ARA 290 averts tissue injury, decreases inflammation and triggers healing." (2)

"As shown in Fig. 4A a significant increase of lipid peroxides was observed in diabetic control group (Group II) when related to the normal control animals (Group I). Administration of ARA290 to diabetic rats (group III and group IV) meaningfully decreased the levels of lipid peroxides which are similar to that of diabetic control group (Group II). As shown in Fig. 4B the activities of enzymic antioxidants SOD, CAT, GPx and GST in the serum of all animal groups were measured. As compared to normal group, diabetic control group (Group II) triggered considerable decrease for all the antioxidant enzymes. However, administration of ARA290 to diabetic rats (group III and group IV) showed antioxidant activity by reinstating the antioxidants enzymes, near to normality. Both 10% and 20% treated diabetic rats (group III and group IV) showed considerable enhancement in activity of antioxidants when compared to diabetic control group (Group II)... As shown in Table 3, the inflammatory markers activity (NF-κβ, TNF-α, IL-6 and IL-10) was noticeably increased in diabetic control rats (Group II) compared to the levels in normal control rats (Group I). While, Page 10/24 the treated diabetic rats with 10% and 20% ARA290 (group III and group IV) significantly decreased the induction of inflammatory markers activity." (2)

ARA-290 Effects on Glucose, Insulin, and Lipids.

"Diabetic control group (Group II) revealed meaningful rises in blood glucose levels from day 1 in compared to normal control group (Group I). The administration of ARA290, 10% and 20% treated diabetic animals (Group III and IV) considerably decreased glucose levels as compared with diabetic control group. After 14 days, the insulin levels in serum of diabetic control group (Group II) were decreased meaningfully as compared with normal control rats (Group I). Treatment with 10% and 20% ARA290 to diabetic rats (group III and group IV) appeared a considerable increase in insulin levels when compared to diabetic control group (Group II). There was a significant decrease in serum lipid levels (TC, TG and LDL), while HDL level was notably increased in diabetic control group (Group II) when compared to normal control animals (Group I). Treatment with 10% and 20% ARA290 to diabetic rats (group III and group IV) appeared a considerable decrease in LDL, TC and TG levels and increase in HDL level when compared to diabetic control group (Group II)." (2)

References

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