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Hinokitiol is a natural bioactive compound found in several aromatic and medicinal plants. It is a terpenoid synthetized and secreted by different species as secondary metabolites. This volatile compound was tested and explored for its different biological properties. In this review, we report the pharmacological properties of hinokitiol by focusing mainly on its anticancer mechanisms. Indeed, it can block cell transformation at different levels by its action on the cell cycle, apoptosis, autophagy via inhibiting gene expression and dysregulating cellular signaling pathways. Moreover, hinokitiol also exhibits other pharmacological properties, including antidiabetic, anti-inflammatory, and antimicrobial effects. It showed multiple and several effects through its inhibition, interaction and/or activation of the main cellular targets inducing these pathologies.

p-cymene also known as p-cymol or p-isopropyltoluene is an alkyl-substituted aromatic compound naturally occurring in essential oils (EOs) of various aromatic plants, including the genus of Artemisia, Protium, Origanum, and Thymus. It is related to the family of terpenes, especially monocyclic monoterpenes. p-cymene is also present in several food-based plants such as carrots, orange juice, grapefruit, tangerine, raspberries and several spices. Numerous studies have demonstrated the pharmacological properties of the monoterpenes p-cymene, including antioxidant, anti-inflammatory, antiparasitic, antidiabetic, antiviral, antitumor, antibacterial, and antifungal activities. The p-cymene has also been reported to act as an analgesic, antinociceptive, immunomodulatory, vasorelaxant and neuroprotective agent. Its anticancer effects are related to some mechanisms such as the inhibition of apoptosis and cell cycle arrest. In this review, we critically highlighted the in vitro and in vivo pharmacological properties of the p-cymene molecule, providing insight into its mechanisms of action and potential applications in drug discovery. In light of this finding, in-depth in vivo studies are strongly required to validate the safety and beneficial effects of the p-cymene molecule in human healthcare and industrial applications as a potential source of drug discovery.

Ethnopharmacological relevance Daphne gnidium L., (Lazaz or Metnan) is a perennial plant that grows around the Mediterranean basin, in Southern Europe, North Africa and the Middle East. It is used in different countries for hair care and to treat several diseases including skin cancer, diabetes, nervous breakdowns, sinusitis, poisoning, rheumatic disorders, odontalgia, muscular pain, and gastrointestinal infections. It is also used as anti-inflammatory, insecticide, and anti-parasitic remedy. Aim of the review In this review, previous studies on D. gnidium including its botanical description, taxonomy, geographical distribution, medicinal use, phytochemistry, and pharmacological properties were critically highlighted and discussed for suggesting the exploration of this specie and its bioactive compounds in medical applications. Materials and methods Data on D. gnidium were gathered from Scientific search engines including PubMed, ScienceDirect, SpringerLink, Web of Science, Scopus, Wiley Online, SciFinder, and Google Scholar. Reports on D. gnidium written in English published before September 2020 were summarized. Results In traditional medicine, D. gnidium is used to treat diabetes, gastrointestinal infections, skin cancer, nervous breakdowns, and sinusitis. The extracts and essential oil of D. gnidium exhibited several biological properties such as antibacterial, antifungal, antiviral, antigenotoxic, hemolytic, anti-inflammatory, immunomodulatory, neuroprotective, allelopathic, and insecticidal effects. Phytochemical investigations identified several chemical classes of secondary metabolites in D. gnidium essential oil and extracts including terpenoids, coumarins, flavonoids, fatty acids, and alkanes. Conclusions The findings presented in this study showed a link between the traditional medicinal use and scientific biological results about D. gnidium. However, further investigations should be carried out to support medical and cosmetic applications of this species. Indeed, D. gnidium and its main compounds should be confirmed concerning their safety and their bioavailability. Moreover, pharmacodynamic studies should be conducted to support their efficacy in medical applications.