Neuroprotective Effects of Carnosic Acid: Insight into Its Mechanisms of Action

Abstract

Carnosic acid is a diterpenoid abundantly present in plants belonging to the genus Rosmarinus and Salvia of the family Lamiaceae, accounting for their application in traditional medicine. The diverse biological properties of carnosic acid that include antioxidant, anti-inflammatory, and anticarcinogenic activities have instigated studies on its mechanistic role, providing further insights into its potential as a therapeutic agent. Accumulating evidence has established the relevance of carnosic acid as a neuroprotective agent exhibiting therapeutic efficacy in combatting neuronal-injury-induced disorders. The physiological importance of carnosic acid in the mitigation of neurodegenerative disorders is just beginning to be understood. This review summarizes the current data on the mode of action through which carnosic acid exerts its neuroprotective role that may serve to strategize novel therapeutic approaches for these debilitating neurodegenerative disorders.

Carnosic Acid Shows Higher Neuroprotective Efficiency than Edaravone or Ebselen in In Vitro Models of Neuronal Cell Damage

“…Neuroprotective effects of natural and synthetic antioxidants such as ED, EB, and CA have been widely documented, and the intracellular mechanisms of their action are rather well recognized [ 20 , 24 , 26 , 27 , 28 , 42 , 43 ]. However, our comparative in vitro study using various neuronal cell models and experimental settings only to some extent supported the general view on the biosafety of these compounds as well as the high efficacy of them in protecting neuronal cells against various harmful insults.…”

“…It should be added that the importance of glia cells in CA-mediated protection was also highlighted in previous studies [ 65 , 70 ]. When taking into account the potential usefulness of CA in the treatment of neurodegenerative diseases [ 28 , 71 ], it is justified to consider it as an active component of nanodrugs, which could balance its unfavorable pharmacokinetic profile [ 12 ]. To this end, it has been reported that nanocarrier-packaged CA ameliorated glia-mediated neuroinflammation and improved cognitive function in an Alzheimer’s disease model [ 72 ].…”

“…EB and its analogues showed neuroprotective effects in various experimental models against cell damage induced by oxygen and glucose deprivation (OGD), amyloid β(1-42), lipopolysaccharide, 6-hydroxydopamine (6-OHDA), and in MPTP-treated mice [ 22 , 23 , 24 , 25 , 26 ]. Carnosic acid (CA, 4aR,10aS)-5,6-dihydroxy-7-isopropyl-1,1-dimethyl-1,3,4,9,10,10a-hexahydro-2H-phenanthrene-4a-carboxylic acid, Figure 1 C) isolated from rosemary (Rosmarinus officinalis) and common sage (Salvia officinalis) possesses antioxidative, anti-inflammatory, and anti-neoplastic properties [ 27 , 28 , 29 ]. CA was found to ameliorate oxidative stress-, glutamate-, and hypoxia-induced injury of neuronal as well as displayed neuroprotective activity in in vitro and in vivo models of Parkinson’s or Alzheimer’s disease [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ].…”

RAGE Inhibitors in Neurodegenerative Diseases

“…It was demonstrated that the use of a citrus flavonoid, nobiletin, attenuated the methylglyoxal-induced toxicity [ 87 ]. Other polyphenolic compounds, including ss-caryophyllene and carnosic acid, and camellia oil were also demonstrated to show anti-inflammatory activity and thus act as potential neuroprotective compounds [ 85 , 88 , 89 ]. The RAGE-induced activation of CD5L, an inflammatory protein, leads to the decreased brain volumes, while higher circulating soluble RAGE (s-RAGE), which functions as a decoy receptor for RAGE, was associated with increased brain volumes in AD models [ 90 ].…”

The Use of Ultrasound-Assisted Maceration for the Extraction of Carnosic Acid and Carnosol from Sage (Salvia officinalis L.) Directly into Fish Oil

“…Carnosic acid and its derivatives are one of the strongest natural antioxidants produced by some plant species. Carnosic acid also exhibits antibacterial, antifungal, antiviral, anti-inflammatory, anticancer and neuroprotective properties [ 1 , 2 , 3 ]. It can also be a preventive and supportive measure in the treatment of many diseases, including Alzheimer’s, Parkinson’s and COVID-19 [ 4 ] as well as some cancers [ 2 ].…”