Chemical composition and anti-oxidant potential on essential oils of Thymus quinquecostatus Celak. from Loess Plateau in China, regulating Nrf2/Keap1 signaling pathway in zebrafish

Abstract

Chemical profile and antioxidant potency of essential oils (EOs) of Thymus quinquecostatus celak. (thyme oils) obtained from Loess Plateau in China had been studied. 130 constituents of thyme oils were determined using gas chromatography-mass spectrometry (GC-MS) and carvacrol ethyl ether was firstly reported as a new natural product, which has been used as a synthetic flavoring substance with no safety concern. The thyme oils showed the anti-oxidant activity using 2,2 diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS), ferric reducing antioxidant power (FRAP) and thiobarbituric acid reactive substances (TBARS) and conferred protection against oxidative stress in zebrafish. In addition, a class of carvacrol analogues was found to develop as potential natural antioxidant products of thyme oils from Loess Plateau by the correlation analysis. YL-thyme oil performed the best antioxidant activity in this research, which could be recommended as preferred sources of thyme oils. Furthermore, YL-thyme oil exhibited a potent antioxidant capacity by reactive oxygen species (ROS) scavenging, enhancing the endogenous antioxidant system, inhibiting lipid peroxidation and activation of Keap1/Nrf2 pathway in zebrafish. Oxidative stress is a phenomenon associated with pathogenetic mechanisms of several diseases including atherosclerosis, neurodegenerative diseases, cancer, diabetes mellitus, inflammatory diseases, as well as psychological diseases or aging processes. It is defined as an imbalance between production of free radicals and reactive metabolites, so-called oxidants or ROS 1. Most of ROS such as superoxide anion (O 2−), hydroxyl radical (OH •), hydrogen peroxide (H 2 O 2) and organic peroxides, are generated in the cells by mitochondrial respiratory chain 2. Excessive ROS can damage cell functionality as they can harm cellular lipids, proteins and DNA 3. The organism contains a complex and carefully balanced cascade of antioxidant enzymes, of which the superoxide dismutase (SOD) and catalase (CAT) are regarded as the first line of the antioxidative enzyme system against ROS such as superoxide and H 2 O 2 generated during oxidative stress 4. The kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2 (Keap1/Nrf2) signaling pathway plays a central role in protecting the body from oxidative damage. The Nrf2 transcription factor is tightly regulated by the repressor protein, Keap1, in the cytoplasm. Under oxidative stress, Nrf2 is released from the Nrf2/

Insecticidal and Repellent Activity of Thymus quinquecostatus Celak. Essential Oil and Major Compositions against Three Stored‐Product Insects

“…According to researches research, carvacrol was one of the characteristic components of Thymus plants. Carvacrol was founded in T. quinquecostatus EO from Loess Plateau [15] . However, carvacrol was not found in the EO collected from Yantai, China.…”

“…Records of the medicinal use of T. quinquecostatus can be traced back to the Song Dynasty (A. D. 960–1279). At present, T. quinquecostatus is widely used to treat stroke, cold, dyspepsia, toothache, acute gastroenteritis, hypertension, chronic eczema and other diseases as folk medicines and was used alone or in combination with other herbal medicines for cancer treatment [15,16] . T. quinquecostatus has antioxidative effects that can mediate the inflammatory response and prevent cell damage through its antioxidant activities [17] .…”

Thymus vulgaris Essential Oil Protects Zebrafish against Cognitive Dysfunction by Regulating Cholinergic and Antioxidants Systems

“…By inhibiting lipid peroxidation and activation of the Keap1/Nrf2 pathway in zebrafish, Thymus quinquecostatus Celak. oils have provided protection against oxidative stress in zebrafish, as demonstrated by He et al [81]. TEO treatment effectively restored the antioxidant defense mechanism by increasing the antioxidant levels of activity in the brain.…”

Teratogenic, Oxidative Stress and Behavioural Outcomes of Three Fungicides of Natural Origin (Equisetum arvense, Mimosa tenuiflora, Thymol) on Zebrafish (Danio rerio)

“…Additionally, a previous study has shown that Thymol exhibits a lower toxicity (3× higher LC 50 of 42.35 μM~6.36 mg L −1 ) [ 19 ] in comparison to the current study, which could be explained by different species’ sensitivities among different laboratories. Notwithstanding, craniofacial and skeletal deformities were similarly observed at higher concentrations (50 μM~7.5 mg L −1 [ 19 ] and 40 mg L −1 [ 20 ]), further supporting the teratogenic potential of Thymol to zebrafish embryos, even at lower concentrations. During embryogenesis, cells acquire distinct functions and specific positions, giving rise to a functional, complex, and multicellular organism through a set of early molecular and cellular mechanisms [ 41 ].…”

“…For instance, horsetail ( Equisetum arvense ) was the first approved basic substance according to the European Regulation (EC) 1107/2009 [ 13 ], but, although not considered as a substance of concern, it has been associated with potential neurodevelopmental toxicity [ 14 ]. Likewise, “jurema preta” ( Mimosa tenuiflora ) has been described as teratogenic to higher vertebrates [ 15 , 16 ], and Thymol, the main monoterpene phenol isolated from plants from the Lamiaceae family such as Thymus vulgaris L. [ 17 ], has been shown to cause developmental abnormalities in chicken and zebrafish embryos [ 18 , 19 , 20 ] and to regulate cholinergic and antioxidant systems in cognitive dysfunctional zebrafish [ 21 ]. However, although current research shows its antifungal properties [ 17 , 22 , 23 ] and some commercial pesticide products based on natural compounds are available on the market, there is a lack of sufficient neurodevelopmental information, and further studies are needed to clarify their environmental risk to non-target organisms to define efficient and appropriate use patterns.…”