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Objective(s): Hyperglycemia, a prevalent metabolic condition observed in diabetes, leads to oxidative damage, inflammatory responses, and other consequences. Natural compounds alleviate the adverse impacts of diabetes. We aimed to explore the effects of alpha-pinene (AP) as a monoterpene on oxidative damage and inflammation caused by high glucose (HG) in the human hepatocellular liver carcinoma (HepG2) cell line. Materials and Methods: The HepG2 cells were subjected to non or HG concentration (50 mM) and treated with or without AP (8, 16, and 32 μg/ml) for 48 hr. The effect of treatments on cellular viability, malondialdehyde (MDA), glutathione (GSH), and activity of anti-oxidant enzymes, including glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), was determined. The gene expression levels of nuclear factor-κβ (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and dipeptidyl peptidase-4 (DPP-4) were estimated using quantitative real-time polymerase chain reaction (qRT-PCR). Results: HG exposure significantly increased cell death, MDA formation, and depletion of GSH content and GPx, CAT, and SOD activity (P

Objective(s): Hyperglycemia, a prevalent metabolic condition observed in diabetes, leads to oxidative damage, inflammatory responses, and other consequences. Natural compounds alleviate the adverse impacts of diabetes. We aimed to explore the effects of alpha-pinene (AP) as a monoterpene on oxidative damage and inflammation caused by high glucose (HG) in the human hepatocellular liver carcinoma (HepG2) cell line. Materials and Methods: The HepG2 cells were subjected to non or HG concentration (50 mM) and treated with or without AP (8, 16, and 32 µg/ml) for 48 hr. The effect of treatments on cellular viability, malondialdehyde (MDA), glutathione (GSH), and activity of anti-oxidant enzymes, including glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), was determined. The gene expression levels of nuclear factor-κβ (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and dipeptidyl peptidase-4 (DPP-4) were estimated using quantitative real-time polymerase chain reaction (qRT-PCR). Results: HG exposure significantly increased cell death, MDA formation, and depletion of GSH content and GPx, CAT, and SOD activity (P<0.05). We have also seen a significant induction in NF-κB, TNF-α, IL-6, and DPP-4 gene expression in hepatocytes under HG conditions (P<0.05). Interestingly, co-treatment with AP in a dose-dependent manner improved cell death and altered levels of MDA and GSH, and activity of GPx and CAT (P<0.05). AP could also modulate the gene expression of NF-κB and inflammatory biomarkers dose-dependently (P<0.05). Conclusion: Our findings suggested the protective effect of AP on hepatocytes under HG conditions through attenuating oxidative stress markers and suppression of inflammatory pathways. [ABSTRACT FROM AUTHOR]

Objective(s): Renal and testicular disorders are primarily associated with oxidative damage and inflammation. Here, alpha-pinene (a type of monoterpene) was investigated for its effect on oxidative/nitrosative stress and the expression of inflammatory and apoptotic factors in the kidneys and testes of rats treated with CCl4.Materials and Methods: CCl4 was injected intraperitoneally (IP) at a dose of 2 ml/kg (twice a week for six weeks). Alpha-pinene (50 mg/kg/day, IP) was also treated during the same period. Results: CCl4 increased the level of malondialdehyde (P

Schizophrenia (SCZ) is a profound neurological disorder that affects approximately 1% of the global population. Alpha-pinene (α-pinene) is a natural and active monoterpene found in coniferous tree oil, primarily pine, with diverse pharmacological characteristics, including antioxidative, anxiolytic, and antidepressant properties. This research study delves into the neuroprotective effects of α-pinene on oxidative stress, memory deficits, and depressive and anxiety-like behaviors in a ketamine-induced mice model of SCZ using male mice. The mice were randomly divided into six groups: vehicle, control, positive control, ketamine, α-pinene at 50 mg/kg, and α-pinene at 100 mg/kg. Treatment of the ketamine-induced mice model of SCZ with α-pinene yielded significant improvements in depressive and anxiety-like behaviors and cognitive impairments. Furthermore, it significantly elevated glutathione (GSH) levels, total antioxidant capacity (TAC), dopamine levels, catalase (CAT), and superoxide dismutase (SOD) activities while markedly reducing malondialdehyde (MDA) levels. The current study establishes that α-pinene treatment effectively mitigates oxidative damage, cognitive deficits, and depressive and anxiogenic-like behaviors in the brains of ketamine-treated mice. Therefore, α-pinene treatment is an efficacious approach to forestall the neurobehavioral and neurobiochemical adverse effects of the ketamine-induced SCZ model of mice.

Objective(s): Renal and testicular disorders are primarily associated with oxidative damage and inflammation. Here, alpha-pinene (a type of monoterpene) was investigated for its effect on oxidative/nitrosative stress and the expression of inflammatory and apoptotic factors in the kidneys and testes of rats treated with CCl4. Materials and Methods: CCl4 was injected intraperitoneally (IP) at a dose of 2 ml/kg (twice a week for six weeks). Alpha-pinene (50 mg/kg/day, IP) was also treated during the same period. Results: CCl4 increased the level of malondialdehyde (P<0.01 in the kidney and P<0.001 in the testis) and nitric oxide (P<0.001 in the kidney and P<0.01 in the testis) and decreased the levels of glutathione (P<0.05) in the kidneys and testicles of rats. CCl4 also reduced the catalase enzyme activity in the kidneys (P<0.05) but did not affect its activity in the testis. In addition, CCl4 enhanced the mRNA expression of TNF-α (P<0.01), nuclear factor-κB (P<0.05), and Bax (P<0.05 in the kidney and P<0.01 in the testis) and decreased the expression of Bcl-2 (P<0.05) in both organs. Alphapinene prevented all the mentioned changes, but it did not influence the expression of Bcl-2 in the kidneys of rats receiving CCl4. Conclusion: Alpha-pinene may have the potential to prevent renal and testicular diseases by strengthening the antioxidant system in the kidneys and testis, and inhibiting oxidative/nitrosative stress, inflammation, and apoptosis caused by CCl4. [ABSTRACT FROM AUTHOR]

T‐cell acute leukemia and lymphoma have a poor prognosis. Although new therapeutic agents have been developed, their therapeutic effects are suboptimal. α‐Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic malignancies. This report provides a comprehensive analysis of the potential benefits of using α‐pinene as an antitumor agent for the treatment of T‐cell tumors. We found that α‐pinene inhibited the proliferation of hematologic malignancies, especially in T‐cell tumor cell lines EL‐4 and Molt‐4, induced mitochondrial dysfunction and reactive oxygen species accumulation, and inhibited NF‐κB p65 translocation into the nucleus, leading to robust apoptosis in EL‐4 cells. Collectively, these findings suggest that α‐pinene has potential as a therapeutic agent for T‐cell malignancies, and further investigation is warranted. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the potential anticarcinogenic effects of three phytochemicals, namely Alpha-pinene (AP), Gamma-terpinene (GT), and P-cymene (PC), on melanoma cells (A2058 cell line). Additionally, the study aims to explore the synergistic activities of these phytochemicals with Dacarbazine, a chemotherapy drug. To understand the molecular mechanism involved in apoptosis induction in the A-2058 cell line, it was used AO/EB staining for apoptosis detection and cell cycle analysis, monitored through flow cytometry. It also determined the mRNA expression levels of different apoptosis-regulatory genes, including p53, Bax, NF-kB, Bcl-2, Bcl-xl, and caspase-3. The antitumor activities of these phytochemicals and their combinations were investigated in a subcutaneous mouse tumor model. The tumor diameter was 21.4 ± 1.1 mm in the Dacarbazine treatment group and 42.4 ± 3.1 mm in the control group. The antitumoral activities of AP and PC in the tumor model were similar to those of Dacarbazine. On the other hand, GT exhibited remarkable antitumoral activity, with a 1.75-fold reduction in tumor diameter compared to the Dacarbazine group. When different combinations of phytochemicals and Dacarbazine were used, the GT plus Dacarbazine treatment group was found to have a 3.5-fold reduction in tumor diameter compared to the Dacarbazine group. The tumor diameters in the Dacarbazine, AP plus GT, GT plus Dacarbazine, and AP plus Dacarbazine treatment groups were 21.4 ± 1.1, 7.6 ± 2.2, 8.6 ± 0.5, and 6.2 ± 1.9 mm, respectively.

Background and Aim: Huntington's disease is a chronic hereditary disorder that causes cognitive and movement defects in affected individuals by progressive destruction of neurons in the cerebral cortex, striatum and the hippocampus. Studies have shown that increased activity of cyclin-dependent kinase-5 (CDK5) plays an important role in the pathogenesis and occurrence of memory impairment in Huntington's disease. Recently, alpha-pinene has been reported to improve learning and memory performance in Alzheimer's and Parkinson's models. Therefore, the aim of this study was to investigate the effect of alpha-pinene on passive avoidance memory and CDK5 gene expression in Huntington's animal model induced by 3-nitro-propionic acid (3-NP). Materials and Methods: In this study, 40 male rats were randomly divided into 5 groups: sham, 3-NP (10 mg/kg),and 3 other groups receiving 3-NP (10 mg/kg) + alpha-pinene at doses of 1, 5 and 10 mg/kg (for 3 weeks,via intraperitoneal injection). Passive avoidance memory was assessed through the shuttle box device. Then, the expression level of CDK5 gene was measured by RT-qPCR method in brain cortex and hippocampus. Results: 3-NP injection caused memory impairment by decreasing step through latency (STL). Alpha-pinene at all three doses improved passive avoidance memory performance. Also, 3-NP injection caused a significant increase in CDK5 gene expression level in the brain cortex and hippocampus compared to that in the sham group. The groups which received alpha-pinene at doses of 5 and 10 mg/kg in brain cortex and 1 mg/kg in hippocampus showed decreased expression level of this gene compared to the group that received 3-NP. Conclusion: The results of this study showed that alpha-pinene improves passive avoidance memory performance probably by reducing the CDK5 gene expression level in Huntington's animal model induced by 3-NP.

Abstract Neonatal hypoxia has a negative impact on the developing brain during the sensitive period. Inflammation plays a key role in the physiological response to hypoxic stress. Considering the anti-inflammatory properties of alpha-pinene, which has received a lot of attention in recent years, in this research we focused on the impact of alpha-pinene on the behavioral responses and proinflammatory factors in rats subjected to the neonatal hypoxia. This study involved Wistar rats (7-day-old) that were divided into six experimental groups, including a control group, groups receiving different doses of alpha-pinene (5 and 10 mg/kg), a hypoxia group receiving 7% O2 and 93% N2, 90 min duration for 7 days, and groups receiving alpha-pinene 30 min before hypoxia. All injections were done intraperitoneally. The rats were evaluated for proinflammatory factors 24 h after exposure to hypoxia (PND14) and at the end of the behavioral test (PND54). The results showed that hypoxia led to decreased motor activity, coordination, and memory, as well as increased inflammation. However, the rats that received alpha-pinene showed improved behavioral responses and reduced inflammation compared to the hypoxia group (all cases p

Purpose: Testicular toxicity is one of the most important side effects of cisplatin (CP) therapy. Alpha-pinene (AP) is a naturally occurring monoterpene with antioxidant character in plants. Here, we aimed to evaluate the therapeutic activity of AP against CP-induced testicular toxicity by including the nuclear factor erythroid 2-associated factor 2 (Nrf2) pathway in rats. Methods: Thirty male rats were divided into 5 groups: control, CP, CP + AP (5 and 10 mg/kg) and only AP (10 mg/kg). CP was administered intraperitoneally at a dose of 5 mg/kg on the first day, followed by three consecutive injections of AP. Serum reproductive hormone levels were evaluated using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers in testicular tissue were also determined colorimetrically. In addition, how CP affects Nrf2 pathway and the effect of AP on this situation were also addressed. Results: Treatment with CP significantly increased OS, inflammation, ERS and apoptosis in testicular tissue. Administrations of AP resulted in an amelioration of these altered parameters. The mechanism of therapeutic effect of AP appeared to involve induction of Nrf2. Furthermore, these results were also confirmed by histological data. Conclusion: Results suggest that AP can exhibit therapeutic effects against CP-induced testicular toxicity. It can be concluded that AP may be a potential molecule to abolish reproductive toxicity after chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Trichomoniasis is one of the most common sexually transmitted infections worldwide. The growing concern of drug resistance of this infection has cautioned the need for new drug development. We evaluated the potential antiproliferative and apoptotic effect of a-pinene and tannic acid (TA) on Trichomonas vaginalis cells. In addition, the cytotoxicity of agents on Vero cells was investigated. Methods: Trichomonas cells were axenically cultured in TYI-S-33 medium. In vitro antiproliferative activity of a-pinene, TA, and metronidazole was investigated against Trichomonas cells. The assays were carried out in triplicate using microtiter plate and trypan blue staining method. Annexin V/PI staining with flow cytometry was used to evaluate apoptosis induction. In addition, the cytotoxic effect was measured by MTT assay. Results: α-Pinene and TA exhibited significant inhibition of the Trichomonas cells and the lowest IC50 values were 22.9 µg/ml and 140 µg/ml at 48 hours' incubation, respectively. The CC50 was found at 116 μg/ml for β-pinene and 473 μg/ml for TA, after 48 hours of treatment. The flow cytometry study demonstrated that the natural compounds induced apoptosis in Trichomonas cells. After 24 hours of treatment, the induction of apoptosis was 5.2% - 36.6% at concentrations of 3.9 - 62.5 μg/ml for β-pinene and TA induced-apoptosis was 6.1% - 53.8% at concentrations of 125-2000 μg/ml. Conclusion: Although the results show the antiproliferative and apoptotic effect of a-pinene and TA on Trichomonas cells, in vivo studies are needed to further clarify the effects of these compounds. [ABSTRACT FROM AUTHOR]

Background: Trichomoniasis is one of the most common sexually transmitted infections worldwide. The growing concern of drug resistance of this infection has cautioned the need for new drug development. We evaluated the potential antiproliferative and apoptotic effect of α-pinene and tannic acid (TA) on Trichomonas vaginalis cells. In addition, the cytotoxicity of agents on Vero cells was investigated. Methods: Trichomonas cells were axenically cultured in TYI-S-33 medium. In vitro antiproliferative activity of α-pinene, TA, and metronidazole was investigated against Trichomonas cells. The assays were carried out in triplicate using microtiter plate and trypan blue staining method. Annexin V/PI staining with flow cytometry was used to evaluate apoptosis induction. In addition, the cytotoxic effect was measured by MTT assay. Results: α-Pinene and TA exhibited significant inhibition of the Trichomonas cells and the lowest IC50 values were 22.9 µg/ml and 140 µg/ml at 48 hours’ incubation, respectively. The CC50 was found at 116 μg/ml for α-pinene and 473 μg/ml for TA, after 48 hours of treatment. The flow cytometry study demonstrated that the natural compounds induced apoptosis in Trichomonas cells. After 24 hours of treatment, the induction of apoptosis was 5.2% - 36.6% at concentrations of 3.9 - 62.5 μg/ml for α-pinene and TA induced-apoptosis was 6.1% - 53.8% at concentrations of 125-2000 μg/ml. Conclusion: Although the results show the antiproliferative and apoptotic effect of α-pinene and TA on Trichomonas cells, in vivo studies are needed to further clarify the effects of these compounds.

Triple-negative breast cancer (TNBC) accounts for approximately 20% of all breast cancer cases and is characterized by a lack of estrogen, progesterone, and human epidermal growth factor 2 receptors. Current targeted medicines have been unsuccessful due to this absence of hormone receptors. This study explored the efficacy of Tulbaghia violacea , a South African medicinal plant, for the treatment of TNBC metastasis. Extracts from T. violacea leaves were prepared using water and methanol. However, only the water-soluble extract showed anti-cancer activity and the effects of this water-soluble extract on cell adhesion, invasion, and migration, and its antioxidant activity were assessed using MCF-10A and MDA-MB-231 cells. The T. violacea extract that was soluble in water effectively decreased the movement and penetration of MDA-MB-231 cells through the basement membrane in scratch and invasion tests, while enhancing their attachment to a substance resembling an extracellular matrix. The sample showed mild-to-low antioxidant activity in the antioxidant assy. Nuclear magnetic resonance spectroscopy revealed 61 chemical components in the water-soluble extract, including DDMP, 1,2,4-triazine-3,5(2H,4H)-dione, vanillin, schisandrin, taurolidine, and α-pinene, which are known to have anti-cancer properties. An in-depth examination of the transcriptome showed alterations in genes linked to angiogenesis, metastasis, and proliferation post-treatment, with reduced activity in growth receptor signaling, angiogenesis, and cancer-related pathways, such as the Wnt, Notch, and PI3K pathways. These results indicate that T. violacea may be a beneficial source of lead chemicals for the development of potential therapeutic medicines that target TNBC metastasis. Additional studies are required to identify the precise bioactive chemical components responsible for the observed anti-cancer effects.

The purpose of this study is to investigate the potential anticarcinogenic effects of three phytochemicals, namely Alpha-pinene (AP), Gamma-terpinene (GT), and P-cymene (PC), on melanoma cells (A2058 cell line). Additionally, the study aims to explore the synergistic activities of these phytochemicals with Dacarbazine, a chemotherapy drug. To understand the molecular mechanism involved in apoptosis induction in the A-2058 cell line, it was used AO/EB staining for apoptosis detection and cell cycle analysis, monitored through flow cytometry. It also determined the mRNA expression levels of different apoptosis-regulatory genes, including p53, Bax, NF-kB, Bcl-2, Bcl-xl , and caspase-3. The antitumor activities of these phytochemicals and their combinations were investigated in a subcutaneous mouse tumor model. The tumor diameter was 21.4 ± 1.1 mm in the Dacarbazine treatment group and 42.4 ± 3.1 mm in the control group. The antitumoral activities of AP and PC in the tumor model were similar to those of Dacarbazine. On the other hand, GT exhibited remarkable antitumoral activity, with a 1.75-fold reduction in tumor diameter compared to the Dacarbazine group. When different combinations of phytochemicals and Dacarbazine were used, the GT plus Dacarbazine treatment group was found to have a 3.5-fold reduction in tumor diameter compared to the Dacarbazine group. The tumor diameters in the Dacarbazine, AP plus GT, GT plus Dacarbazine, and AP plus Dacarbazine treatment groups were 21.4 ± 1.1, 7.6 ± 2.2, 8.6 ± 0.5, and 6.2 ± 1.9 mm, respectively., Competing Interests: No conflict interest., (© 2024 Published by Elsevier Ltd.)

Objective: Increased mupirocin use leads to mupirocin resistance and is associated with persistence of methicillin-resistant Staphylococcus aureus (MRSA) carriers, prolonged hospitalization, and significant economic burdens for health systems. The study aimed to investigate the antimicrobial activity of compounds of Salvia rosmarinus L. ("rosemary", formerly Rosmarinus officinalis), alone or in combination with mupirocin, against multidrug resistant MRSA using isolates obtained from pediatric patients., Methods: The in vitro antibacterial activity of the monoterpene α-pinene (α-Pi), a rosemary essential oil constituent, alone and in combination with mupirocin, was evaluated by determining the minimum inhibitory concentrations and minimum bactericidal concentrations (MBCs) and the fractional inhibitory concentration indices (FICIs) and fractional bactericidal concentration indices against multidrug-resistant clinical MRSA strains. The in vivo efficacy of α-Pi, alone and in combination with mupirocin, to eradicate MRSA infection was determined using an optimized mouse model of MRSA-infected wounds. Mouse skin samples (obtained via biopsy) were assessed for toxicity, and rabbit skin samples for irritation., Results: Both in vitro and in vivo, α-Pi was active against MRSA strains and acted synergistically with mupirocin against MRSA strains. Mupirocin-monoterpene combinations exhibited FICI values of 0.2 to 0.4, reducing the MBC of topical mupirocin 33-fold. A topical formulation containing α-Pi and mupirocin enhanced the efficacy of mupirocin in an in vivo MRSA-infected mouse skin model without significantly harming the skin of mice and rabbits., Conclusions: A topical formulation combining mupirocin and α-Pi may aid in the development of innovative agents for treating MRSA infections.

The absolute photoionization cross section of the monoterpenoid, alpha-pinene (AP), is presented together with the relative photoionization cross sections of its dissociative fragments for the first time. Experiments are performed via multiplexed vacuum ultraviolet (VUV) synchrotron photoionization (PI) mass spectrometry in the 8.0-11.0 eV energy range. Experimental work is conducted at the Advanced Light Source of the Lawrence Berkeley National Laboratory. Dissociative fragments were identified at m/z 121, 94, 93, 92, and 80. The photoionization cross section for the parent mass at 11.0 eV was determined to be 17±4 Mb with a total ionization cross section of 92±23 Mb at the same photon energy. Experimental appearance energies of dissociative ionization fragments and potential dissociative ionization pathways calculated at the G4 level of theory are presented as well., (© 2024 Wiley-VCH GmbH.)

Schizophrenia (SCZ) is a profound neurological disorder that affects approximately 1% of the global population. Alpha-pinene (α-pinene) is a natural and active monoterpene found in coniferous tree oil, primarily pine, with diverse pharmacological characteristics, including antioxidative, anxiolytic, and antidepressant properties. This research study delves into the neuroprotective effects of α-pinene on oxidative stress, memory deficits, and depressive and anxiety-like behaviors in a ketamine-induced mice model of SCZ using male mice. The mice were randomly divided into six groups: vehicle, control, positive control, ketamine, α-pinene at 50 mg/kg, and α-pinene at 100 mg/kg. Treatment of the ketamine-induced mice model of SCZ with α-pinene yielded significant improvements in depressive and anxiety-like behaviors and cognitive impairments. Furthermore, it significantly elevated glutathione (GSH) levels, total antioxidant capacity (TAC), dopamine levels, catalase (CAT), and superoxide dismutase (SOD) activities while markedly reducing malondialdehyde (MDA) levels. The current study establishes that α-pinene treatment effectively mitigates oxidative damage, cognitive deficits, and depressive and anxiogenic-like behaviors in the brains of ketamine-treated mice. Therefore, α-pinene treatment is an efficacious approach to forestall the neurobehavioral and neurobiochemical adverse effects of the ketamine-induced SCZ model of mice., Competing Interests: The authors declare that they have no known competing financial and personal relationships with other individuals or institutions that could affect their investigation reported in this paper., (© 2024 The Authors.)

Objectives: Renal and testicular disorders are primarily associated with oxidative damage and inflammation. Here, alpha-pinene (a type of monoterpene) was investigated for its effect on oxidative/nitrosative stress and the expression of inflammatory and apoptotic factors in the kidneys and testes of rats treated with CCl 4 ., Materials and Methods: CCl 4 was injected intraperitoneally (IP) at a dose of 2 ml/kg (twice a week for six weeks). Alpha-pinene (50 mg/kg/day, IP) was also treated during the same period., Results: CCl 4 increased the level of malondialdehyde ( P <0.01 in the kidney and P <0.001 in the testis) and nitric oxide ( P <0.001 in the kidney and P <0.01 in the testis) and decreased the levels of glutathione ( P <0.05) in the kidneys and testicles of rats. CCl 4 also reduced the catalase enzyme activity in the kidneys ( P <0.05) but did not affect its activity in the testis. In addition, CCl 4 enhanced the mRNA expression of TNF-α ( P <0.01), nuclear factor-κB (P<0.05), and Bax ( P <0.05 in the kidney and P <0.01 in the testis) and decreased the expression of Bcl-2 ( P <0.05) in both organs. Alpha-pinene prevented all the mentioned changes, but it did not influence the expression of Bcl-2 in the kidneys of rats receiving CCl 4 ., Conclusion: Alpha-pinene may have the potential to prevent renal and testicular diseases by strengthening the antioxidant system in the kidneys and testis, and inhibiting oxidative/nitrosative stress, inflammation, and apoptosis caused by CCl 4 ., Competing Interests: None.