Review

References__________________________________________________________________________

Salehi B, Upadhyay S, Erdogan Orhan I, Kumar Jugran A, L D Jayaweera S, A Dias D, Sharopov F, Taheri Y, Martins N, Baghalpour N, Cho WC, Sharifi-Rad J. Therapeutic Potential of α- and β-Pinene: A Miracle Gift of Nature. Biomolecules. 2019 Nov 14;9(11):738. doi: 10.3390/biom9110738. 

Abstract. α- and β-pinene are well-known representatives of the monoterpenes group, and are found in many plants' essential oils. A wide range of pharmacological activities have been reported, including antibiotic resistance modulation, anticoagulant, antitumor, antimicrobial, antimalarial, antioxidant, anti-inflammatory, anti-Leishmania, and analgesic effects. This article aims to summarize the most prominent effects of α- and β-pinene, namely their cytogenetic, gastroprotective, anxiolytic, cytoprotective, anticonvulsant, and neuroprotective effects, as well as their effects against H2O2-stimulated oxidative stress, pancreatitis, stress-stimulated hyperthermia, and pulpal pain. Finally, we will also discuss the bioavailability, administration, as well as their biological activity and clinical applications.

Han EJ, Choi EY, Jeon SJ, Moon JM, Lee SW, Lee JH, Jung GH, Han SH, Jung SH, Yang MS, Jung JY. Anticancer Effects of α-Pinene in AGS Gastric Cancer Cells. J Med Food. 2024 Apr;27(4):330-338. doi: 10.1089/jmf.2023.K.0267. 

Abstract. Gastric cancer is the fifth most common cancer globally and the third leading cause of cancer-related mortality. Existing treatment strategies for gastric cancer often present numerous side effects. Consequently, recent studies have shifted toward devising new treatments grounded in safer natural substances. α-Pinene, a natural terpene found in the essential oils of various plants, such as Lavender angustifolia and Satureja myrtifolia, displays antioxidant, antibiotic, and anticancer properties. Yet, its impact on gastric cancer remains unexplored. This research assessed the effects of α-pinene in vitro using a human gastric adenocarcinoma cell-line (AGS) human gastric cancer cells and in vivo via a xenograft mouse model. The survival rate of AGS cells treated with α-pinene was notably lower than that of the control group, as revealed by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay. This decline in cell viability was linked to apoptosis, as verified by 4',6-diamidino-2-phenylindole and annexin V/propidium iodide staining. The α-pinene-treated group exhibited elevated cleaved-poly (ADP-ribose) polymerase and B cell lymphoma 2 (Bcl-2)-associated X (Bax) levels and reduced Bcl-2 levels compared with the control levels. Moreover, α-pinene triggered the activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 within the mitogen-activated protein kinase (MAPK) pathway. In the xenograft mouse model, α-pinene induced apoptosis through the MAPK pathway, devoid of toxicity. These findings position α-pinene as a promising natural therapeutic for gastric cancer.

Sarria S, Wong B, García Martín H, Keasling JD, Peralta-Yahya P. Microbial synthesis of pinene. ACS Synth Biol. 2014 Jul 18;3(7):466-75. doi: 10.1021/sb4001382. 

Abstract. The volumetric heating values of today's biofuels are too low to power energy-intensive aircraft, rockets, and missiles. Recently, pinene dimers were shown to have a volumetric heating value similar to that of the tactical fuel JP-10. To provide a sustainable source of pinene, we engineered Escherichia coli for pinene production. We combinatorially expressed three pinene synthases (PS) and three geranyl diphosphate synthases (GPPS), with the best combination achieving ~28 mg/L of pinene. We speculated that pinene toxicity was limiting production; however, toxicity should not be limiting at current titers. Because GPPS is inhibited by geranyl diphosphate (GPP) and to increase flux through the pathway, we combinatorially constructed GPPS-PS protein fusions. The Abies grandis GPPS-PS fusion produced 32 mg/L of pinene, a 6-fold improvement over the highest titer previously reported in engineered E. coli. Finally, we investigated the pinene isomer ratio of our pinene-producing microbe and discovered that the isomer profile is determined not only by the identity of the PS used but also by the identity of the GPPS with which the PS is paired. We demonstrated that the GPP concentration available to PS for cyclization alters the pinene isomer ratio.

Hou J, Zhang Y, Zhu Y, Zhou B, Ren C, Liang S, Guo Y. α-Pinene Induces Apoptotic Cell Death via Caspase Activation in Human Ovarian Cancer Cells. Med Sci Monit. 2019 Sep 4;25:6631-6638. doi: 10.12659/MSM.916419. 

Abstract. Background. The plant-derived terpenoid, alpha-pinene is a bicyclic monoterpene potentially useful for the treatment of various diseases which also includes cancer and its types. The present investigation is about finding the anticancer activity of the alpha-pinene extracted from the leaves of Boswellia dalzielii over the PA-1 cancer cells of the human ovary. MATERIAL AND METHODS The cytotoxic activity of the alpha-pinene was evaluated using MTT and LDH assays which indicated that alpha-pinene could induce cytotoxicity in cancer-causing cells in the ovary. The consequences of alpha-pinene on the cell sequence regulation were determined by the staining technique using propidium iodide (PI) followed with flow cytometry. RESULTS The cell cycle distribution analysis showed that alpha-pinene inhibit the cycle progression from G₂ to M phase. In addition, apoptosis analysis is done through the double staining investigation using Annexin V-FITC/PI to analyze the controlled growth of alpha-pinene which is associated with the apoptosis. Caspase-3 a crucial enzyme involved in apoptosis was markedly increased in the a-pinene treated PA-1 cells. The apoptosis results reveal, that the cancer cells at the human ovary with alpha-pinene induces the significant populations of apoptotic cells. CONCLUSIONS Overall, alpha-pinene may exert anticancer effects in PA-1 cells by promoting cytotoxicity, suppression of cell sequence progression along with the programmed cell death.