Oral supplementation with ursolic acid ameliorates sepsis-induced acute kidney injury in a mouse model by inhibiting oxidative stress and inflammatory responses

Abstract

Ursolic acid (UA) as a multiple bioactive native compound has recently been demonstrated to treat sepsis in animal models. However, the beneficial effects of UA in sepsis-induced acute kidney injury (AKI) are not completely understood. In the present study, the effect of UA on sepsis-induced AKI in cecal ligation and puncture (CLP) surgery mice was investigated. Renal histomorphological analysis was performed by hematoxylin and eosin staining. The expression of inflammatory markers in the kidney of septic mice was measured by reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that UA administration improved survival in septic mice induced by CLP surgery. The treatment with UA revealed protection against AKI induced by CLP surgery, including the alleviation of glomerular damage and vacuolization in the proximal tubules. In addition, the effects of UA on oxidative stress and inflammation in septic mice were determined. The findings suggested that UA may protect against sepsis-induced AKI by inhibiting reactive oxygen species and inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β and IL-6, in the kidney from septic mice. Finally, UA inhibited CLP-induced activation of nuclear factor-κB signaling in the kidney from septic mice. The findings of the present study demonstrated that UA may be used as a potential therapeutic agent for complications of sepsis, especially for sepsis-induced AKI.

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…(cranberry), Arctostaphylos uva-ursi (L.) Spreng (bearberry), Rhododendron hymenanthes Makino, Eriobotrya japonica, Rosemarinus officinalis, Calluna vulgaris, Eugenia jambolana and Ocimum sanctum, as well as in the wax-like protective coatings of fruits such as pears, apples and prunes [265]. UA has numerous biochemical and pharmacological effects including antiinflammatory, anti-oxidative, anti-proliferative, anti-atherosclerotic, anti-leukemic, anti-viral, and anti-diabetic effects [266][267][268][269][270][271][272]. It also exerts anti-cancer activities in ovarian, breast, gastric, prostate, lung, liver, bladder, pancreatic, and colorectal cancers [273][274][275][276][277][278][279][280][281].…”

Antioxidant and Anti-inflammatory Mechanisms of Neuroprotection by Ursolic Acid: Addressing Brain Injury, Cerebral Ischemia, Cognition Deficit, Anxiety, and Depression

“…Other anti-inflammatory and antioxidant actions of UA were in the mouse model of allergic asthma [141], cigarette smoke-induced emphysema in rats as chronic obstructive pulmonary disease (COPD) [142], and the LPS-induced lung injury in mice [143]. The 2,4,6-trinitrobenzenesulfonic acid- (TNBS-) induced colitis (colon shortening and myeloperoxidase (MPO) activity) model in the mouse model [144]; sepsis-induced acute kidney injury via inhibition of ROS and inflammatory cytokines, including TNF- α , IL-1 β , and IL-6 in the kidney from septic mice [145]; sepsis induced in rats by cecal ligation and puncture [146]; LPS-induced acute inflammation model [147]; and various other multiple mechanisms including NF- κ B and STAT3 inhibition [148] have been demonstrated. All these data support the anti-inflammatory mechanisms through inhibition of key inflammatory cytokines, COX and iNOS expressions, and antioxidant mechanisms including the activation of the Nrf2 pathway.…”

Untitled

“…As an example, one study found that ursolic acid, one of the compounds in bearberry leaf extract, was able to ameliorate acute kidney injury associated with sepsis in mice. 24 A thorough review of the potential impact of each of these supplements on the patient's clinical presentation is beyond the scope of this work.…”

“…While the prevalence of CD is approximated to be one percent of the American population, it can be as high as four percent in those with cryptogenic transaminase elevation. 2,24 It has been demonstrated that patients with unexplained infertility, recurrent miscarriage or IUGR have a respective 5-, 6-or 8-fold risk of being afflicted by CD compared to the general population. 25 Additionally, patients with these reproductive disorders often do not present with the classic symptomology of CD.…”