Effects of thymoquinone on acute corneal and orofacial pains in rats: central involvement of opioid, cannabinoid, muscarinic cholinergic, and serotonin receptors
Volume 17, Issue 3, March 2026, Pages 175-181
Esmaeal Tamaddonfard, Amir Erfanparast, Afsaneh Niakani
Abstract Thymoquinone (TQ), the bioactive compound found in black seed, possesses beneficial properties. In the present study, the effects of oral administration of TQ were investigated on acute corneal and orofacial pains in rats. To clarify the central mechanism of action, muscarinic cholinergic, cannabinergic 1 (CB1) and 5-hydroxytryptamine receptor antagonists were delivered into the 4th ventricle of the brain after oral administration of TQ. Acute corneal and orofacial pains were induced by dropping of hypertonic saline (50.00 µL; 5.00 M) on the corneal surface and subcutaneous injection of capsaicin (1.50 µg; 20.00 µL) in the vibrissal pad, respectively. The eye wiping number and face rubbing duration were recorded as corneal and orofacial pains behavioral responses, respectively. Locomotor activity was measured using an open-field test. The TQ (5.00 mg kg-1) had no effects, while it reduced pain responses at 10.00, 20.00, and 40.00 mg kg-1. Intracerebro-ventricular injections of naloxone (an antagonist of opioid receptors), (N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (an antagonist of CB1 receptors), atropine (an antagonist of muscarinic cholinergic receptors), and ondansetron (an antagonist of 5-hydroxytryptamine 3 receptors) at a similar dose of 10.00 µg kg-1 inhibited corneal and orofacial pains suppression caused by 40.00 mg kg-1 TQ. The tested drugs did not affect locomotor activity. It is concluded that TQ caused analgesia in the acute corneal and orofacial pains. Central opioid, cholinergic muscarinic, CB1, and 5-hydroxytryptamine 3 receptors might be involved in the anti-nociceptive effects of TQ.
Thymoquinone attenuates paw incision-induced spontaneous and evoked pain through anti-oxidative and anti-inflammatory mechanisms in rats
Volume 16, Issue 2, February 2025, Pages 89-96
Seyed Siavash Ghoreishi, Saeed Azizi, Esmaeal Tamaddonfard, Safiyeh Aghazadeh
Abstract Surgery commonly causes post-operative pain that should be alleviated to prevent complications. In addition to the use of synthetic drugs, there has been a widespread desire to use medicinal plants for surgical pain management. Thymoquinone (TQ), a constituent of Nigella sativa black seeds, exhibits a potent anti-oxidant property. Celecoxib (CLX), a potent non-steroidal anti-inflammatory drug, is widely used in pain management. In the present study, the effects of TQ and CLX on pain caused by hind paw surgical incision were compared. Fifty-six rats were divided into four groups of 14 rats as intact, vehicle, TQ, and CLX groups. In each group, six rats were planned to record pain-related behaviors on days 1 - 10 and eight rats were designed for determination of serum biochemical alterations on days 1 (four rats) and 3 (four rats) after surgery. Oral administrations of TQ and CLX at a same dose of 10.00 mg kg-1 alleviated paw lifting number (spontaneous pain) and paw withdrawal threshold evoked by von Frey filaments on metal mesh floor, improved the decreased contents of serum total anti-oxidant capacity and superoxide dismutase, and restored the increased levels of serum malondialdehyde and tumor necrosis factor-alpha. The results suggested that TQ by employing anti-oxidant and anti-inflammatory mechanisms, might relieve the pain induced by hind paw plantar incision, being comparable with CLX.
Protective effects of Nigella sativa oil, thymoquinone and dexamethasone on bleomycin-induced lung fibrosis in rats
Volume 15, Issue 11, November 2024, Pages 613-620
Farid Saghghaei, Ali Rassouli, Goudarz Sadeghi-Hashjin, Farhang Sasani, Mohammad Kazem Koohi
Abstract Pulmonary fibrosis (PF) is a chronic interstitial lung disease with a progressive damage to the air sacs and deposition of collagen fibers in the lung tissue. The study aimed to explore the effects of Nigella sativa oil (NSO) or thymoquinone (TQ), alone or in combination with dexamethasone (DEX), on the development of bleomycin (BLM)-induced PF. Forty-two male rats were divided into seven groups: Control (CTRL); BLM, received a single dose of BLM on day 0, intratracheally; all remaining groups received BLM, as well. DEX, received DEX daily, intraperitoneally, 1 day before BLM and continued for 14 days; NSO and TQ groups, received daily NSO and TQ, respectively, 7 days before BLM and continued for 35 days; DEX + TQ, received both DEX and TQ; DEX + NSO, received both DEX and NSO. At the end, lung tissues were used for histopathological and biochemical analyses. BLM significantly increased the severity of fibrosis and inflammation compared to the CTRL. Bleomycin also significantly increased the amount of hydroxyproline, however, decreased most antioxidant enzymes in the lung tissue compared to the other groups. Group TQ + DEX significantly reduced the severity of BLM-induced PF as well as alterations in biochemical parameters, lung weight and O2 saturation. Nigella sativa oil slightly reduced BLM-induced PF, however, it caused non-significant hyperemia in lung tissue. Thymoquinone potentiated the effects of DEX on most biochemical and pathological alterations of BLM-induced lung injury much better than NSO. More studies are needed to support the use of NSO and TQ as potential protective agents against PF.
Effect of thymoquinone on acetic acid-induced visceral nociception in rats: role of central cannabinoid and α2-adrenergic receptors
Volume 15, Issue 3, March 2024, Pages 131-138
Somayyeh Naderi, Esmaeal Tamaddonfard, Saeid Nafisi, Farhad Soltanalinejad-Taghiabad
Abstract Thymoquinone (TQ) is the main biologically active substance of Nigella sativa (black seeds). It has anti-cancer, anti-inflammatory, anti-diabetic, anti-oxidative and anti-nociceptive properties. This study was aimed to explore the effect of TQ on acetic acid-induced visceral nociception. The central mechanisms of the effect of TQ were investigated using cannabinergic (AM251) and α2-adrenergic (yohimbine [Yoh]) antagonists. The lateral ventricle of the brain was cannulated for intracerebroventricular (ICV) injections. Visceral nociception was induced by intra-peritoneal (IP) injection of acetic acid (1.00% in a volume of 1.00 mL). Measuring the latency time to the first writhing appearance and counting the number of writhing in 5-min intervals for a period of 60 min were performed. Locomotor activity was determined using an open-field test. Oral administration (PO) of 2.50 and 10.00 mg kg-1 TQ increased the latency time to the first writhing appearance and decreased the number of writhing. The AM251 (5.00 µg per rat; ICV) and Yoh (5.00 µg per rat; ICV) partially prevented TQ (10.00 mg kg-1; PO)-induced anti-nociception. Locomotor activity was not altered by these treatments. The results of the present study showed that TQ had the ability to reduce visceral nociception caused by IP injection of acetic acid. The central mechanisms of this action of TQ might be partially mediated by cannabinergic and α2-adrenegic receptors.
