Research Title: Ononis spinosa Alleviated Capsaicin-Induced Mechanical Allodynia in a Rat Model through TRPV1 Modulation.

Author: Sahar Majdi Jaffal, Published Year: 2021

Korean Journal of pain. , 34 (3):1-9.

Faculty: Science

Abstract: Background Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel implicated in pain sensation in response to heat, protons, and capsaicin (CAPS). It is well established that TRPV1 is involved in mechanical allodynia. This study investigates the effect of Ononis spinosa (Fabaceae) in CAPS-induced mechanical allodynia and its mechanism of action. Methods Mechanical allodynia was induced by the intraplantar (ipl) injection of 40 µg CAPS into the left hind paw of male Wistar rats. Animals received an ipl injection of 100 µg O. spinosa methanolic leaf extract or 2.5% diclofenac sodium 20 minutes before CAPS injection. Paw withdrawal threshold (PWT) was measured using von Frey filament 30, 90, and 150 minutes after CAPS injection. A molecular docking tool, AutoDock 4.2, was used to study the binding energies and intermolecular interactions between O. spinosa constituents and TRPV1 receptor. Results The ipsilateral ipl injection of O. spinosa before CAPS injection increased PWT in rats at all time points. O. spinosa decreased mechanical allodynia by 5.35-fold compared to a 3.59-fold decrease produced by diclofenac sodium. The ipsilateral pretreatment with TRPV1 antagonist (300 µg 4-[3-Chloro-2-pyridinyl]-N-[4-[1,1-dimethylethyl] phenyl]-1-piperazinecarboxamide [BCTC]) as well as the β2-adrenoreceptor antagonist (150 µg butoxamine) attenuated the action of O. spinosa. Depending on molecular docking results, the activity of the extract could be attributed to the bindings of campesterol, stigmasterol, and ononin compounds to TRPV1. Conclusions O. spinosa alleviated CAPS-induced mechanical allodynia through 2 mechanisms the direct modulation of TRPV1 and the involvement of β2 adrenoreceptor signaling.

Keywords: Butoxamine, Capsaicin, Fabaceae, Hyperalgesia, Molecular Docking Simulation, Neuralgia, Ononis, Pain, Stigmasterol, TRPV Cation Channels

Research Title: Ononis spinosa Alleviated Capsaicin-Induced Mechanical Allodynia in a Rat Model through TRPV1 Modulation.

Author: Sahar Majdi Jaffal, Published Year: 2021

Korean Journal of pain. , 34 (3):1-9.

Faculty: Science

Abstract: Background Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel implicated in pain sensation in response to heat, protons, and capsaicin (CAPS). It is well established that TRPV1 is involved in mechanical allodynia. This study investigates the effect of Ononis spinosa (Fabaceae) in CAPS-induced mechanical allodynia and its mechanism of action. Methods Mechanical allodynia was induced by the intraplantar (ipl) injection of 40 µg CAPS into the left hind paw of male Wistar rats. Animals received an ipl injection of 100 µg O. spinosa methanolic leaf extract or 2.5% diclofenac sodium 20 minutes before CAPS injection. Paw withdrawal threshold (PWT) was measured using von Frey filament 30, 90, and 150 minutes after CAPS injection. A molecular docking tool, AutoDock 4.2, was used to study the binding energies and intermolecular interactions between O. spinosa constituents and TRPV1 receptor. Results The ipsilateral ipl injection of O. spinosa before CAPS injection increased PWT in rats at all time points. O. spinosa decreased mechanical allodynia by 5.35-fold compared to a 3.59-fold decrease produced by diclofenac sodium. The ipsilateral pretreatment with TRPV1 antagonist (300 µg 4-[3-Chloro-2-pyridinyl]-N-[4-[1,1-dimethylethyl] phenyl]-1-piperazinecarboxamide [BCTC]) as well as the β2-adrenoreceptor antagonist (150 µg butoxamine) attenuated the action of O. spinosa. Depending on molecular docking results, the activity of the extract could be attributed to the bindings of campesterol, stigmasterol, and ononin compounds to TRPV1. Conclusions O. spinosa alleviated CAPS-induced mechanical allodynia through 2 mechanisms the direct modulation of TRPV1 and the involvement of β2 adrenoreceptor signaling.

Keywords: Butoxamine, Capsaicin, Fabaceae, Hyperalgesia, Molecular Docking Simulation, Neuralgia, Ononis, Pain, Stigmasterol, TRPV Cation Channels

Research Title: TRP channels in COVID-19 disease: Potential targets for prevention and treatment.

Author: Sahar Majdi Jaffal, Published Year: 2021

Chemico-Biological Interactions. , 245 (109567): 1-11.

Faculty: Science

Abstract: Coronavirus disease 2019 [COVID-19] is a global health threat caused by severe acute respiratory syndrome coronavirus 2 [SARS-CoV2] that requires two proteins for entry: angiotensin-converting enzyme 2 [ACE2] and -membrane protease serine 2 [TMPRSS2]. Many patients complain from pneumonia, cough, fever, and gastrointestinal (GI) problems. Notably, different TRP channels are expressed in various tissues infected by SARS-CoV-2. TRP channels are cation channels that show a common architecture with high permeability to calcium [Ca2+] in most sub-families. Literature review shed light on the possible role of TRP channels in COVID-19 disease. TRP channels may take part in inflammation, pain, fever, anosmia, ageusia, respiratory, cardiovascular, GI and neurological complications related to COVID-19. Also, TRP channels could be the targets for many active compounds that showed effectiveness against SARS-CoV-2. Desensitization or blocking TRP channels by antibodies, aptamers, small molecules or venoms can be an option for COVID-19 prevention and future treatment. This review provides insights into the involvement of TRP channels in different symptoms and mechanisms of SARS-CoV-2 , potential treatments targeting these channels and highlights missing gaps in literature.

Keywords: COVID-19; Prevention; SARS-CoV-2; Symptoms; TRP channels; Treatment.

Research Title: Anti-inflammatory and antipyretic potential of Arbutus andrachne L. methanolic leaf extract in rats.

Author: Sahar Majdi Jaffal, Published Year: 2021

Asian Pacific Journal of Tropical Biomedicine, 11(11): 491-499.

Faculty: Science

Abstract: Abstract Objective: To explore the anti-inflammatory and antipyretic effects of methanolic leaf extract from Arbutus andrachne and its mechanism of action. Methods: Paw edema was induced by intraplantar (i.pl.) injection of λ-carrageenan (1% w/v, 100 μL/paw) while pyrexia was evoked by intraperitoneal (i.p.) injection of 20?ker's yeast (20 mL/kg body wt) in male Wistar rats. The anti-inflammatory and antipyretic effects of Arbutus andrachne methanolic leaf extract were explored by injecting rats with different doses of the plant extract (150, 300, and 600 mg/kg body wt, i.p.). Selective antagonists for transient receptor potential vanilloid-1 (TRPV1), cannabinoid receptor 1 (CB1), and alpha-2 adrenergic receptor (a2-AR) were used to unravel the extracts’ mechanism of action. Blood samples were collected from the heart of rats to measure the levels of interleukin-6 (IL-6) and prostaglandin E2 (PGE2) by enzyme-linked immunosorbent assay. Results: The extract exhibited potent anti-inflammatory activity by decreasing paw thickness and IL-6 levels. In addition, yeast-evoked pyrexia was attenuated by the extract treatment via TRPV1 and CB1 receptors and a reduction in PGE2 levels. No significant effects were found for a2-AR. Moreover, the rats that received the plant extract demonstrated similar responses to the positive control group. Conclusions: Arbutus andrachne can be a good candidate for treating inflammation and pyrexia and should be further investigated.

Keywords: Arbutus andrachne; Anti-inflammatory; Antipyretic; PGE2; IL-6; TRPV1; CB1; a2-ARs

Research Title: Effect of explant type and different plant growth regulators on callus induction and growth in citrus sinensis (l.) osbeck.

Author: Sahar Majdi Jaffal, Published Year: 2022

South Western Journal of Horticulture, Biology and Environment, 13(1), 1-12.

Faculty: Science

Abstract: In this study, we analyzed the effect of using different explants (zygotic embryos, leaves, stems, and cotyledons) on callus induction and the effect of different PGRs on the growth response of the callus. The results showed that callogenesis was faster when all explants were incubated in the dark than in light incubation. Maximum callus induction was observed in zygotic embryos (compared to other explants) and in the group cultured in 3 mg/L 2,4 D and 1 mg/L 6- BAP combination. Similarly, 3 mg/L 2,4 D and 1 mg/L BAP PGRs were also the effective concentrations for callus induction from cotyledons and leaves. However, a 2 mg/L 2,4 D and 1 mg/L BAP combination was the most potent in inducing callus from stems. In addition, our results indicated that the best hormonal combination for callus multiplication of callus derived from zygotic embryos was 1 mg/L 2,4 D and 1 mg/L BAP. The inhibition of ethylene activity improved callus growth during the multiplication stage in two groups being treated with 1 mg/L 2,4 D alone or with 2 mg/L 2,4 D in combination with 1 mg/L BAP. In contrast, ethylene synthesis inhibitors had insignificant effects on callus multiplication in any of the groups cultured in different PGRs combinations. The calluses obtained in all treated groups were friable, loose, and had a white to yellow color.

Keywords: Citrus sinensis, 6-benzyl amino purine, 2,4 dichloro phenoxy acetic acid, callus, ethylene.

Research Title: Evaluation of the antiproliferative effect of selected plant extracts on colon and skin cancer cell lines.

Author: Sahar Majdi Jaffal, Published Year: 2022

Journal of Applied Pharmaceutical Science, , 12 (11):91-96.

Faculty: Science

Abstract: The aim of this study was to assess the antiproliferative effect of extracts obtained from medicinal plants that grow wild in Jordan against the human melanoma (WM136-1A) and colon cancer (Caco-2 cancer) cell lines using fibroblast cell lines as control cells. The selected plants are Varthemia iphionoides (Asteraceae), Micromeria myrtifolia (Lamiaceae), Micromeria nervosa (Lamiaceae), Origanum dayi (Lamiaceae), Ajuga chia (Lamiaceae), Salvia palaestina (Lamiaceae), and Bongardia chrysogonum (Berberidaceae). The results showed that M. nervosa and O. dayi exhibited antiproliferative activity against Caco-2 cancer cell line, with half-maximal inhibitory concentrations (IC50) that equal 98 ± 2.5 and 73.6 ± 3.4 μg/ml, respectively. Furthermore, A. chia, B. chrysogonum, and O. dayi exhibited antiproliferative activity against the WM136-1A cancer cell line, with IC50 that equals 400 ± 5.1, 98.1 ± 3.2, and 245 ± 3.6 μg/ml, respectively. None of the extracts had an effect on fibroblast cells at any used concentration. In conclusion, the extracts of M. nervosa, O. dayi, A. chia, and B. chrysogonum showed promising antiproliferative potential and can be good candidates for the development of novel anticancerous agents.

Keywords: Medicinal plants, Jordan, anti-proliferation

Research Title: Imbalances of key parameters needed for energy-yielding processes in the serum of tramadol-treated male rats.

Author: Sahar Majdi Jaffal, Published Year: 2022

Journal of applied pharmaceutical Science, 12(4): 153-158.

Faculty: Science

Abstract: Addiction is one of the major health challenges in the world. Tramadol is an analgesic that has been widely abused, causing negative health consequences. This study sheds light on the effect of the administration of tramadol hydrochloride (HCl) on the serum levels of key parameters needed for energy production. Male Wistar rats received oral administration of tramadol HCl for 30 days and then were sacrificed to collect blood from the eyes and determine the levels of nutritional measures in the serum by kits. Our findings showed that the daily oral gavage of 50 or 100 mg/kg tramadol HCl for a month decreased the serum levels of ferrous iron and glucose significantly compared to the nontreated rats. Additionally, both doses increased the levels of total protein, triglycerides, and magnesium compared to the nontreated animals. Only the dose of 50 mg/kg tramadol HCl was effective in elevating the serum concentration of vitamin B12. Moreover, tramadol HCl treatment did not trigger any change in the levels of zinc in comparison to the control group. In conclusion, tramadol causes imbalances of key parameters needed for energy production.

Keywords: Addiction, tramadol, rats, energy

Research Title: The role of adenosine receptor ligands on inflammatory pain: Possible modulation of TRPV1 receptor function.

Author: Sahar Majdi Jaffal, Published Year: 2023

Inflammopharmacology, 31: 337-347.

Faculty: Science

Abstract: Chronic pain has a debilitating consequences on health and lifestyle. The currently available analgesics are often ineffective and accompanied by undesirable adverse effects. Although adenosine receptors (AR) activation can affect nociceptive, inflammatory, and neuropathic pain states, the specific regulatory functions of its subtypes (A1, A2A, A2B and A3 ARs) are not fully understood. The aim of this study was to investigate the role of different AR ligands on inflammatory pain. The von Frey filament test was used to assess the anti-nociceptive effects of adenosine ligands on Complete Freund’s Adjuvant (CFA)-induced mechanical allodynia in (180–220 g) adult male Sprague Dawley rats (expressed as paw withdrawal threshold, PWT). Neither the A2AAR selective agonist CGS 21680 hydrochloride (0.1, 0.32 and 1 mg/kg) nor the A2BAR selective agonist BAY 60-6583 (0.1, 0.32 and 1 mg/kg) produced any significant reversal of the PWT. However, the A1AR selective agonist ( ±)-5′-Chloro-5′-deoxy-ENBA, the A3AR selective agonist 2-Cl-IB-MECA, the A2AAR selective antagonist ZM 241385 and the A2BAR selective antagonist PSB 603 produced a significant reversal of the PWT at the highest dose of 1 mg/kg. Co-administration of the selective antagonists of A1AR and A3AR PSB36 (1 mg/ml) and MRS-3777 (1 mg/ml); respectively, significantly reversed the anti-nociceptive effects of their corresponding agonists. Furthermore, calcium imaging studies reveled that the effective AR ligands in the behavioral assay also significantly inhibit capsaicin-evoked calcium responses in cultured rat dorsal root ganglia (DRG) neurons. In conclusion, modulating the activity of the transient receptor potential vanilloid 1 (TRPV1) receptor by ARs ligands could explain their anti-nociceptive effects observed in vivo. Therefore, the cross talk between ARs and TRPV1 receptor may represent a promising targets for the treatment of inflammatory pain conditions.

Keywords: CFA, inflammation, chronic, pain TRPV1

Research Title: Substance Abuse among University Students: Assessing Prevalence, Risk and Preventive Measures.

Author: Sahar Majdi Jaffal, Published Year: 2023

Jordan Journal of Pharmaceutical Science, 16(2): 235-244.

Faculty: Science

Abstract: The study included a survey conducted among 679 students from private and public universities whereby two third of them were females and more than half were studying in medical and health departments. It was found that 7.1% of university students used drugs in their life including illicit drugs, alcohol and cigarettes. Also, the addictive students started using drugs at a mean age of 18 years old ± 3.9. Importantly, around half of the addictive students succeeded to quit using drugs, 20.8% reported not trying to quit, while 33.3% of them tried but could not quit. In addition, the findings of this study revealed that peer pressure (n= 657, 96.8%), and the lack of religious commitment (n= 654, 96.3%), were the most motivational factors for drug abuse. Finally, regression analysis showed that female gender (OR= 0.094, p-value <0.001), and studying in public university (OR= 0.496, p-value= 0.042) were considered protective factors against substance abuse.

Keywords: Students, substance use, knowledge, attitude

Research Title: Effect of Arbutus andrachne L. Methanolic Leaf Extract on TRPV1 Function: Experimental and Molecular Docking Studies.

Author: Sahar Majdi Jaffal, Published Year: 2022

Journal of Applied Pharmaceutical Science, 12(10): 69-77

Faculty: Science

Abstract: Currently used analgesics have several side effects urging the need for new natural sources of therapeutics. Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel and a key receptor in pain. In this study, we explored the effect of a methanolic leaf extract from Arbutus andrachne L. (a medicinal plant growing in Jordan) and its mechanism of action on TRPV1 function and expression. Our findings showed that the extract decreased capsaicin-induced cobalt (Co+2) influx in dorsal root ganglia (DRG) neurons, an effect that involved cannabinoid receptor 1 (CB1) and TRPV1 but not alpha (α)-2 adrenergic receptors. The extract had no effect on capsaicin-evoked TRPV1 expression in the skin, DRGs, spinal cord, and brain. Importantly, the effect of A. andrachne was similar to the responses shown in the positive control group. Additionally, by conducting molecular docking between the ingredients identified in A. andrachne extract and TRPV1 receptor, it was found that α-tocopherol, ursolic acid, and β-sitosterol (similar to TRPV1 antagonist, capsazepine) fit in the same pocket of TRPV1 receptor indicating that these compounds are the active ingredients responsible for the effect of the extract in decreasing capsaicin-induced Co+2 influx. A. andrachne extract decreased capsaicin-induced Co+2 influx significantly and can be a good candidate as an analgesic.

Keywords: Arbutus andrachne, TRPV1, molecular docking, cobalt, influx