Special Issues

The Role of Plant Extracts, Essential Oils and Isolated Phytochemicals in Human Diseases
Editor: Marcello Iriti

Submission Deadline: 31 December 2023 (Status: Open)

Special Issue Editor(s)

Marcello Iriti      Email
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
Interests: bioactive phytochemicals; essential oils; nutraceuticals; phytotherapeutics; functional foods; mediterranean diet; ethnopharmacology; antimicrobials; antimicrobial resistance; one health; cancer chemoprevention; anticancer agents; antineoplastic resistance; cardioprotection; neuroprotection; bioavailability; pharmacokinetics

Special Issue Information

Dear Colleagues,

Preclinical (in vitro and in vivo) studies have highlighted the plethora of biological activities of bioactive phytochemicals, such as antimicrobial, antioxidant/pro-oxidant, anti-inflammatory, and cytotoxic and immunomodulating activities. Plant extracts and essential oils generally possess a multi-target mechanism of action, making them promising antimicrobial, cardioprotective, neuroprotective, anti-cancer, anti-diabetic, anti-obesity, and anti-aging agents. It is possible that phytochemicals can also be used as adjuvant and sensitizing agents for use in combination with conventional [antimicrobial and anticancer] therapies to increase their efficacy, reduce their adverse effects, decrease the risk of selecting resistant microbial strains or cancer cells, and even reverse resistance, including radioresistance. However, despite positive data from cell cultures and animal models for this type of application, the evidence in humans remains incomplete. The efficacy of plant natural products in the prevention and treatment of communicable and non-communicable diseases should be further substantiated on the basis of evidence-based phytotherapy. Indeed, more clinical trials of plant natural products in healthy subjects and subjects with specific diseases are needed to improve the knowledge about their effective dose, route of administration, bioavailability, adverse effects and drug interactions.

Marcello Iriti
Guest Editor


phytotherapeutics; nutraceuticals; ethnopharmacology; antimicrobial resistance; one health; cancer chemoprevention; anticancer agents; antineoplastic resistance; cardioprotection; neuroprotection; bioavailability; pharmacokinetics

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  • Article
    Omkulthom Al kamaly, Ashwag S. Alanazi, Omar Noman, Hamada Imtara
    Journal of Biological Regulators and Homeostatic Agents. 2023, 37(11): 6411-6418. https://doi.org/10.23812/j.biol.regul.homeost.agents.20233711.608
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    Background: Medicinal plants and natural products have proven effective in inhibiting the growth of cancer cells due to their rich content of active compounds, with polyphenols being among the most prominent. This study aims to assess the antiproliferative activity of Heliotropium bacciferum extracts on breast (MCF-7) and lung (A549) cancer cell lines and identify the extract's key active compounds.

    Methods: The antiproliferative activity of Heliotropium bacciferum extract and fractions on breast (MCF-7) and lung (A549) cancer cell lines was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Subsequently, the hexane extract was selected as the most effective extract for investigating the mechanism of its antiproliferative activity on A549 cell lines. The investigation involved the evaluation of cell cycle alterations using propidium iodide staining and the induction of apoptosis using the Annexin V-FITC/PI kit. Finally, gas chromatography/mass spectrometry (GC/MS) analysis was conducted to identify the chemical compounds in the hexane extract of Heliotropium bacciferum.

    Results: According to the MTT assay, the hexane fraction of Heliotropium bacciferum effectively halted the growth of A549 and MCF-7 cancer cells with IC50 values of 104.14 and 83.84 μg/mL, respectively. Additionally, methyl lineoleate (36.5%), linoleic acid (19.1%), and 3′-Acetyllycopsamine (10.7%) were the major components in the Heliotropium bacciferum hexane fraction, according to GC/MS analysis.

    Conclusions: In order to produce pharmaceutical anticancer medicines for cancer therapies, Heliotropium bacciferum hexane fraction can be employed.

  • Article
    Rukayat Abiola Abdulsalam, Jamiu Olaseni Aribisala, Saheed Sabiu
    Journal of Biological Regulators and Homeostatic Agents. 2023, 37(11): 6295-6318. https://doi.org/10.23812/j.biol.regul.homeost.agents.20233711.599
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    Background: The relevance of aminoglycosides has decreased in recent times due to the prevalence of their modifying enzymes, such as aminoglycoside N-acetyltransferases (AAC) [e.g., AAC (6')-ly], aminoglycoside O-nucleotidyltransferases (ANT) [e.g., ANT (2”)] and aminoglycoside O-phosphotransferases (APH) [e.g., APH (3')-IIa)], which inactivate them. However, the recent development of plazomicin, which resists the modifying actions of some subclasses of AAC, ANT, and APH, has sparked renewed interest in aminoglycosides. This study aims to identify computationally potent and less toxic modulators of AAC (6')-ly, ANT (2”), and APH (3')-IIa from Gnaphalium affine (G. affine) that could be used in combinatory therapy with aminoglycosides.

    Methods: Potent and less toxic modulators of the three enzymes were identified using molecular docking, quantitative structure-activity relationship (QSAR) study, pharmacokinetics properties, and a 100 ns molecular dynamic simulation for stability and energy refinement.

    Results: The results show that plazomicin is a potent aminoglycoside-like antibiotic (probability of being active (Pa): 0.803) with significant binding free energies of –51.01, –53.01, and –81.86 kcal/mol against ANT (2”), APH (3')-IIa, and AAC (6')-ly, respectively. The high binding free energy of plazomicin against the three enzymes correlated with its predicted high bioactivity against them. Interestingly, bioprospecting the metabolites of G. affine against the three enzymes revealed that the top-ranked compounds in each case formed thermodynamically stable complexes (root mean square deviation (RMSD): 1.43–2.37 Å) with pharmacokinetic properties that potentiated them as less toxic enzyme inhibitors than plazomicin.

    Conclusions: Overall, the thermodynamic binding free energy and the QSAR analyses identified alpha-cedrol as a putative inhibitor of the three enzymes. The binding free energy of alpha-cedrol ranged from –46.26 to –53.27 kcal/mol, which is comparable to that of plazomicin against ANT (2”) and APH (3')-IIa. Further validation of alpha-cedrol as a novel inhibitor of the investigated enzymes is highly recommended. Both in vitro and in vivo studies should be conducted to confirm this efficacy.

  • Article
    Hayat Bilal, Mubarak Ali Khan, Syed Wadood Ali Shah, Mehreen Ghias, Haya Hussain, Huma Ali, Mehboob Ur Rahman, Muhammad Zahoor, Riaz Ullah, Amal Alotaibi
    Journal of Biological Regulators and Homeostatic Agents. 2023, 37(11): 6231-6245. https://doi.org/10.23812/j.biol.regul.homeost.agents.20233711.594
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    Background: Helicteres isora is a highly valued medicinal plant whose fruits have been traditionally used throughout Asia, Africa, and other parts of the world in treating a variety of diseases, including diabetes mellitus and memory-related health problems. This study aimed to evaluate the in-vitro/in-vivo toxicity and anti-amnesiac profile of Helicteres isora (H. isora) extract.

    Methods: Initially, experimental animals were subjected to acute, sub-chronic, and chronic toxicity evaluation to establish the safety profile of the H. isora-crude (Hi-Crd) extract of selected plant fruit extract. In the first phase, oral administrations of the graded doses of 500, 1000, and 1500 mg/kg body weight (b.w.) were administered to experimental rats for 14 days. In the second phase, higher doses (3000, 4000, and 5000 mg/kg b.w.) were administered to assess acute toxicity. On the 28th day, blood was obtained and subjected to serum biochemical analysis and lipid profiling to evaluate chronic toxicity. To further evaluate the toxicity in deep, histopathology studies of the kidney, liver, and pancreas were performed. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of the extract were also performed, and IC50 values were calculated. The scopolamine-induced amnesic mice were utilized in behavioral studies (Y-maze and Novel Object Recognition Test (NORT)), where doses of 75 and 150 mg/kg b.w. of Hi-Crd were administered to experimental animals.

    Results: In the acute toxicity test, no symptoms of morbidity or toxicity were observed. Hi-Crd increased the relative liver and kidney weight at the end of the sub-chronic toxicity test when given at a dose of 4000 mg/kg b.w.. During the chronic toxicity test, the extract showed substantial effects on several biochemical parameters. Although a rise in the lipid profile was noted, the overall effect on other biochemical parameters was negligible. At day 28, there was no significant effect on the liver enzyme markers, and thus the extract was considered to be safe at tested doses. Hi-Crd has a safe profile in terms of uric acid, bilirubin, and blood urea while there was a slight rise in the serum creatinine level. The H.isora-chloroform fraction (Hi-Chl) showed maximum activity with IC50 values of 54.29 ± 1.17 μg/mL against AChE and 105.66 ± 2.91 μg/mL against BuChE. In behavioral studies, the chloroform extract considerably enhanced spontaneous alteration performance as measured through the Y-maze test (p < 0.001), at tested doses. Its counterpart, the ethyl acetate fraction, also showed noteworthy outcomes with good significance levels; p < 0.01 and p < 0.001 at 75 and 150 mg/kg b.w., respectively. In addition, the chloroform fraction significantly improved the discrimination index (DI) in experimental mice to 67.08% as compared to the amnesic group (29.87%) mice results.

    Conclusions: Helicteres isora Linn was found to be well tolerated during the performed set of tests and could be considered an effective treatment to enhance memory impairment in short- and long-term therapy with an adequate margin of safety. However, the study found that it may have adverse effects to an imperceptible level on kidney and liver functions. Therefore, further studies on other animal models are necessary to confirm its future use as a drug.

  • Article
    Fatima Zahrae Radi, Noureddine Bencheikh, Mohamed Bouhrim, Omar M. Noman, Ramzi A. Mothana, Mansour N. Ibrahim, Mohamed Bnouham, Touriya Zair
    Journal of Biological Regulators and Homeostatic Agents. 2023, 37(11): 6113-6130. https://doi.org/10.23812/j.biol.regul.homeost.agents.20233711.584
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    Background: Aromatic and medicinal plants are a source of biologically active secondary metabolites, such as polyphenols. These substances have several biological properties, such as antioxidant, antimicrobial, and antihyperglycemic activities. This study aims to evaluate the phenolic compound content and antioxidant, antibacterial, antifungal, and antihyperglycemic activities of extracts from two aromatic and medicinal plant species growing wild in the Middle Atlas region of Morocco: Thymus zygis L. and Thymus willdenowii Bois..

    Method: Phytochemical screening was carried out using colorimetric and precipitation reactions. Total polyphenols were determined using the Folin-Ciocalteu reagent, flavonoids by aluminum trichloride (AlCl3), and condensed tannins by vanillin in an acidic medium. Polyphenols were identified by High-Performance Liquid Chromatography (HPLC) and ultraviolet-visible (UV/VIS) detection. Antioxidant activity was assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and Ferric Reducing Antioxidant Power (FRAP) methods. Antimicrobial activity was assessed on six bacterial strains (Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Acinetobacter baumanii (A. baumanii), Shigella dysenteria (Sh. dysenteria), Salmonelle Typhi (S. Typhi), and Enterobacter cloacae (E. cloacae)) by disk diffusion, Minimum Inhibitory Concentration (MIC), and Minimum Bactericidal Concentration (MBC) tests. The oral glucose tolerance test and the α-amylase inhibition test assessed antihyperglycimiant activity.

    Results: The analysis of the aqueous extracts of these plants revealed the existence of polyphenolic compounds, sterols and triterpenes, saponosides, and polyuronides. Furthermore, the quantification of total polyphenols, flavonoids, and tannins showed that the extracts of Thymus zygis (T. zygis) and Thymus willdenowii (T. willdenowii) are rich in these compounds. The DPPH and FRAP antioxidant activity test revealed that our extracts have antioxidant activities against DPPH with an median inhibitory concentration (IC50) of 6.98 ± 0.03 μg/mL and 11.82 ± 0.30 μg/mL, and against FRAP with IC50 of 5.95 ± 0.03 mg/mL and 11.90 ± 0.03 mg/mL for T. zygis and T. willdenowii, respectively. The area under the curve (AUC) of antihyperglycemic activity was significantly lower (p < 0.01) in rats treated with plant extracts 54.76 g/L/h for T. zygis, and 53.21 g/L/h for T. willdenowii, respectively. The antimicrobial activity assay revealed that only T. zygis extract was active starting at a concentration of 10 mg/mL. Acute toxicity results showed that administering these extracts up to the dose limit (2 g/kg) induced non-toxicity or mortality in mice.

    Conclusions: The results show that T. zygis and T. willdenowii decocts have exceptional antioxidant and antihyperglycemic properties to fight against the harmful elements that can weaken the body.

  • Article
    Shadman Ahmad, Khalid Amin, Amin Ullah, Hayat Khan, Izzat Ullah, Iftikhar Ahmed, Alamgir Khan, Mohammed S. Almuhayawi, Soad K. Al Jaouni, Samy Selim, Mutasem Saad Almehayawi, Arshad Farid
    Journal of Biological Regulators and Homeostatic Agents. 2023, 37(11): 5983-5993. https://doi.org/10.23812/j.biol.regul.homeost.agents.20233711.573
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    Background: Medicinal plants are abundant reservoirs of antimicrobial compounds. Medicinal plants, which are rich sources of many possible medications, are used therapeutically by people in different countries. Justicia adhatoda, a widespread perennial shrub in the tropical region of Southeast Asia, is known for expectorant and antispasmodic activity. In the present study, various extracts of Justicia adhatoda leaves and extract-mediated silver nanoparticles (AgNPs) were assessed for antimicrobial potency against a panel of thirteen multi-drug-resistant bacterial strains and seven fungal strains.

    Methods: Various solvent extracts of Justicia adhatoda leaves and extract-mediated AgNPs were prepared and dried. Following incubation, extracts were obtained through the evaporation of solvent. The extracts were also evaluated for various parameters such as moisture contents, extractive value, phytochemical and Fourier transform infrared (FT-IR) analysis. The AgNPs were characterized for size and structure using X-rays diffraction (XRD) and scanning electron microscopy (SEM). Solvent extracts and extract-mediated AgNPs were assessed for their antimicrobial activities using a well diffusion assay.

    Results: The FT-IR and phytochemical analysis revealed various types of bioactive compounds and functional groups such as tannins, reducing sugars, flavonoids, steroids, polysterol, terpenoids, saponins, glycosides, phenols, anthraquinones, and alkaloids. The nanoparticles synthesized were round and spherical in shape, with a size range of 35–45 nm, as demonstrated by XRD and SEM analysis. All the extracts demonstrated comparable activity against the bacterial strains; however, the methanolic extract proved relatively more potent. Among the panel of multidrug-resistance (MDR) bacterial strains, Staph aureus, Klebsiella, Citrobacter and Shigella proved relatively more sensitive towards all solvent extracts. Likewise, all fungal strains were susceptible towards all the extracts, though Helminthosporium and Trichoderma were relatively more susceptible. The antimicrobial activity of the AgNPs was also assessed alone and in combination with standard drugs.

    Conclusion: Various solvent extracts of Justicia adhatoda contain numerous bioactive compounds with antimicrobial activities. Both solvent extracts and extract-mediated AgNPs hold broad-spectrum antimicrobial potential. However, the AgNPs synthesized in the aqueous extract were relatively more potent against bacterial and fungal strains. Herein, the potential of Justicia adhatoda as an antimicrobial agent is demonstrated.

  • Article
    Ahlam Outman, Codjo Hountondji, Ferdinand Kouoh Elombo, Chaima Abidi, Mohamed Bouhrim, Mohammed Al-Zharani, Fahd A. Nasr, Mohammed S. Aleissa, Bernard Gressier, Naïma Nedjar, Bruno Eto
    Journal of Biological Regulators and Homeostatic Agents. 2023, 37(10): 5669-5677. https://doi.org/10.23812/j.biol.regul.homeost.agents.20233710.545
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    Backgrounds: Protein biosynthesis takes place in the ribosome. Some antibiotic and antitumor molecules show more reactivity and affinity with ribosome proteins. These observations encourage the search for protein synthesis inhibitors of targets in the fight against infectious diseases and cancer. This study assessed the utilization of Lepidium sativum (LS) seeds germination in rapidly screening new anticancer candidates for drugs.

    Methods: Antineoplastic prescribed in the clinic was used at different concentrations in the medium of LS seed germination, and the rootlet length was measured after 72 hours.

    Results: The results showed that antineoplastics inhibitors of protein synthesis inhibit the germination of seed rootlets whatever their origin: chemicals (R2 = 0.99), antibiotics (R2 = 0.87), or extracts of medicinal plants (R2 = 0.93). The half maximal inhibitory concentration (IC50) obtained was close to that of cancer cell lines.

    Conclusion: To our knowledge. This is the first demonstration that utilization of seed germination of LS might be used for the rapid screening of new antineoplastics candidates.

  • Article
    Bouchra Soulaimani, Imane Abbad, Ayoub Amssayef, Elena M. Varoni, Marcello Iriti, Nour-Eddine Mezrioui, Lahcen Hassani, Abdelaziz Abbad
    Journal of Biological Regulators and Homeostatic Agents. 2023, 37(10): 5621-5631. https://doi.org/10.23812/j.biol.regul.homeost.agents.20233710.541
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    Background: The present study was conceived to compare the chemical composition and the related antimicrobial activity of essential oils (EOs) obtained from nine commonly used Moroccan lavender species, namely L. mairei, L. multifida, L. tenuisecta, L. maroccana, L. latifolia, L. pedunculata subsp. atlantica, L. stoechas, L. angustifolia and L. dentata. It aimed to classify these widely used Moroccan lavenders, based on their chemical profiles and antimicrobial effectiveness against some human pathogenic microorganisms.

    Methods: Plant aerial parts were steam-distilled and the obtained EOs were initially analyzed using gas chromatography/mass spectrometry (GC/MS), then investigated for their antimicrobial activity against six bacteria and four candida strains, using disc diffusion and broth microdilution methods.

    Results: The chemical analyses showed that all the EOs investigated were classified as oxygenated monoterpene-rich oils (61.78%–92.46%). Hierarchical cluster analysis (HCA) based on the EO chemical compositions enabled the classification of these Moroccan lavender species into four distinct chemical groups: a carvacrol group (Group I), comprising the species L. tenuisecta, L. maroccana and L. mairei, a carvacrol/camphor group (Group II), represented by the species L. multifida, a camphor group (Group III), composed of L. dentata, L. stoechas, L. pedunculata subsp. atlantica, L. latifolia, and a camphor/endo-borneol/1,8 cineole group, represented by L. angustifolia (Group IV). The highest antimicrobial activity was observed for oils obtained from L. tenuisecta, L. maroccana and L. mairei (carvacrol group), with inhibitory zone diameters ranging from 10.30 ± 0.16 to 35.34 ± 0.85 mm, and minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) ranging from 0.039 mg/mL to 5 mg/mL. L. multifida EO (carvacrol/camphor group) showed potent activity, while the lavender EOs from groups III and IV demonstrated the weakest activity.

    Conclusions: These results support the potential use of some native Moroccan lavenders, particularly those characterized by carvacrol and/or carvacrol/camphor rich oils, as promising sources of natural antimicrobials to combat some human infectious diseases.

  • Article
    Neha Sharma, Rasdeep Kour, Kommu Nagaiah, Shafiul Haque, Hardeep Singh Tuli, Sandeep Kaur, Satwinderjeet Kaur
    Journal of Biological Regulators and Homeostatic Agents. 2023, 37(10): 5489-5502. https://doi.org/10.23812/j.biol.regul.homeost.agents.20233710.530
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    Background: Plumbago zeylanica L. (P. zeylanica L.), an ethnomedicinal plant species, is known for its diverse therapeutic benefits, such as anti-malarial, anti-inflammatory, anti-microbial, memory enhancing, and wound-healing properties. This study aimed to investigate the antioxidant, genoprotective, and cytotoxic activities of different root fractions of P. zeylanica L., namely PzMH (hexane fraction), PzMC (chloroform fraction), PzME (ethyl acetate fraction) and PzMM (methanol fraction).

    Methods: The present study involved the investigation of the free radical scavenging potential of all the fractions. Antioxidant activity was assessed through superoxide radical scavenging, nitric oxide radical scavenging, and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assays. Genoprotective efficacy was determined using the alkaline comet assay to evaluate the protective effects against DNA damage induced by hydrogen peroxide (H2O2) in human blood lymphocytes. Additionally, cytotoxicity was investigated against three different cancer cell lines: MCF-7, MDA-MD231 (breast cancer cell lines), and A498 (kidney carcinoma cell line) to examine the suppression of cell proliferation.

    Results: Among all the fractions, PzME exhibited the highest antioxidant activity with IC50 values of 80.94 μg/mL, 79.63 μg/mL, and 98.3 μg/mL in superoxide radical scavenging, nitric oxide radical scavenging, and DPPH assays, respectively. In terms of genoprotective effects, the PzME fraction demonstrated the highest protection against H2O2-induced DNA damage in human blood lymphocytes, reducing the percentage tail DNA content from 29.6% to 7.34% at the highest tested concentration (400 μg/mL). Additionally, the PzME fraction showed potent cytotoxicity against MCF-7 cells, followed by MDA-MB-231 and A498 cells, with 50% growth inhibition at concentrations of 147.95 μg/mL, 225.37 μg/mL, and 226.13 μg/mL, respectively. Phytochemical screening revealed the highest total phenolic, total flavonoid, and total tannin contents in the PzME fraction. GC-MS analysis of the PzME fraction identified trans-cinnamic acid, 2,4-Di-tert-butylphenol, and 2-Methoxy-4-vinylphenol as potential compounds responsible for the observed genoprotective and cytotoxic activities.

    Conclusions: The study highlights the antioxidant, genoprotective, and cytotoxic properties of PzME fraction from Plumbago zeylanica L. root. The fraction exhibited robust antioxidant potential and protected human blood lymphocytes from DNA damage. Additionally, it exhibited notable cytotoxic effects against breast cancer and kidney carcinoma cell lines.

  • Article
    Muhsin Ali, Muhammad Ajmal Khan, Humaira Yasmin, Bakhtawar Khan, Aftab Amin, Ajaz Ahmad, Awais Farid, Amin Ullah, Sadia Butt, Qurban Ali
    Journal of Biological Regulators and Homeostatic Agents. 2023, 37(10): 5213-5232. https://doi.org/10.23812/j.biol.regul.homeost.agents.20233710.505
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    Background: Achyranthes bidentata Blume (Abb) is a renowned medicinal herb in traditional Chinese medicine. The molecular mechanism associated with the anti-diabetic potential of Abb is yet to be determined. In this study, we elucidated the in vivo and in vitro anti-diabetic potential of the methanolic leaf extract of Abb (Abb-ME) in alloxan-induced diabetic mice and HepG2 cells.

    Methods: Qualitative and quantitative phytochemical analysis was performed to identify the metabolites in the Abb-ME. Diabetes mellitus (DM) was induced in mice using alloxan monohydrate (150 mg/kg). Diabetic parameters (blood glucose, body weight, lipid profile, hematological indices, histopathological changes) were observed post Abb-ME administration. The in vitro study included glucose uptake assay and quantitative reverse transcription-PCR (qRT-PCR) analysis of glucose transporters 2 (GLUT2) gene expression in HepG2 cells.

    Results: Qualitative and quantitative phytochemical analysis revealed the presence of alkaloids, flavonoids (44.89 ± 3.9 mg/g extract), carbohydrates, proteins, phenols (60.3 ± 1.2 mg/g extract), and steroids. The results showed that the Abb-ME treatment group (500 mg/kg) exhibited significant (p < 0.05) reductions in blood glucose levels compared to the diabetic control and Glibenclamide group. Other diabetic parameters, such as body weights and lipid profiles, were significantly improved (p < 0.05) in the Abb-ME treated group (500 mg/kg) compared to the diabetic control mice. The altered hematological indices, including packed cell volume (PCV), hemoglobin (Hb), Red Blood Cell (RBC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), Total White Blood Cell (TWBC), and White Blood Cell (WBC) differentials, observed in the diabetic control group were normalized after Abb-ME administration. These findings revealed that Abb-ME treatment effectively resolved several aberrant hematological indices associated with diabetes. Histopathological analysis of mice pancreas confirmed increased acini cell density, β-cell counts, and clear border formations between the endocrine and exocrine regions following Abb-ME treatment. In vitro studies showed significant (p < 0.05) glucose uptake (169.6%, 100 μg/mL) in HepG2 cells following Abb-ME treatment compared to the control (100%). GLUT2 gene expression was increased (1.28-fold) following Abb-ME treatment relative to the control.

    Conclusions: Our data suggest that Abb-ME possesses antidiabetic potential, providing a basis for further studies and applications.

  • Article
    Zahra Taghipour, Maryam Bahmanzadeh, Mahnaz Khanavi, Seyede Nargess Sadati Lamardi, Mojgan Tansaz, Roja Rahimi
    Journal of Biological Regulators and Homeostatic Agents. 2023, 37(9): 4749-4759. https://doi.org/10.23812/j.biol.regul.homeost.agents.20233709.463
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    Background: Polycystic ovary syndrome (PCOS) is the leading cause of infertility induced by ovarian disorders. The promising pharmacological activities of clove buds in gynecological disorders have been mentioned in traditional Persian medicine and in recent studies. Since no studies have been conducted on the role of clove aqueous extract (CAE) in the management of PCOS, this study was designed to evaluate its effects on some biochemical and histopathological parameters in letrozole-induced PCOS in rats.

    Methods: Thirty-six rats were used for this study: 6 were in the control group, and in the other 30, PCOS was induced by letrozole (1 mg/kg/day). After 3 weeks of induction, PCOS was approved by conducting vaginal smears. Then PCOS-induced rats were divided into five groups, letrozole-induced polycystic ovary syndrome (PCOS), clomiphene citrate 1 mg/kg/day (CLO), and CAE50, 100, 200, which received 50, 100, and 200 mg/kg/day of standardized clove aqueous extract based on eugenol, respectively. The treatment kept going for 30 days. Estrous cyclicity, body weight, oxidative stress-related markers, sex hormones, and ovarian histological parameters were measured.

    Results: Disrupted estrous cyclicity, increased body weight, follicular cyst, ovarian level of malondialdehyde (MDA), total oxidant status (TOS), luteinizing hormone (LH), and testosterone levels, as well as decreased estradiol, progesterone, superoxide dismutase (SOD) and total antioxidant capacity (TAC) levels, were demonstrated in PCOS group. The aforementioned parameters were improved following the CAE administration. The estrous phase was observed in the vaginal smear following all doses of CAE administration. The serum level of LH (at doses 50 and 200 mg/kg), LH/follicle-stimulating hormone (FSH) (at all doses), testosterone (at doses 100 and 200 mg/kg) and estradiol (at doses 100 and 200 mg/kg) was significantly decreased. The serum level of progesterone (100 and 200 mg/kg) was increased significantly following CAE administration. Moreover, CAE reduced cystic follicles and ameliorated oxidative parameters.

    Conclusions: In conclusion, clove can be a complementary medicine for PCOS patients, but clinical studies are needed to demonstrate its efficacy and safety.

  • Article
    Zaheer Uddin, Muhammad Zahoor, Syed Wadod Ali Shah, Mehreen Ghias, Muhammad Naveed Umar, Riaz Ullah, Essam A. Ali, Mohammad Attaullah, Sher Wali Khan
    Journal of Biological Regulators and Homeostatic Agents. 2023, 37(9): 4701-4712. https://doi.org/10.23812/j.biol.regul.homeost.agents.20233709.459
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    Background: Diabetes, a disease identified by high glucose levels in the bloodstream, is caused due to irregularities in insulin secretion or its action. These irregularities can have detrimental effects on various organs impacting vision; renal, nerve, and cardiac functions. The aim of the project was to investigate the ameliorative effect of aerial parts of Teucrium royleanum in the form of extracts on the biochemical alterations associated with oxidative stress and hyperglycemia.

    Methods: After extraction and fractionations, the extracts were subjected to antioxidant and antidiabetic potential evaluations against diphenylpicrylhydrazyl (DPPH) free radical and alpha-glucosidase following the standard protocols. The extract was then fed to experimental animals after toxicity evaluations. The animals' blood glucose levels and other blood biochemical parameters, liver function, and renal function parameters were monitored throughout the 28-day treatment period in Streptozotocin (STZ) induced diabetic animals. The oxidative stress markers were also evaluated in the diabetic animal's blood.

    Results: Ethyl acetate extract more potently inhibited DPPH radical and alpha-glucosidase with IC50 values of 76.12 and 55.12 μg mL-1 correspondingly. At the second and third weeks of treatment (14th and 21st day), the groups received Teucrium royleanum crude extract (Tr-Crd) at 150 and 300 mg/kg body weight (b.w), and Teucrium royleanum chloroform fraction (Tr-Chl) and Teucrium royleanum ethyl acetate (Tr-Eta) at 75 and 150 mg/kg b.w exhibited a significant reduction in blood glucose levels. At the end of the 28-day treatment, significant reductions in glucose levels were observed, with values of 138.9 ± 4.6 mg/dL and 115.7 ± 4.6 mg/dL (p < 0.001) for Tr-Eta at doses of 75 and 150 mg/kg b.w doses, respectively, approaching the levels of the normal control group (104.5 ± 5.4 mg/dL). The impact of treatment on the body weight of the rats was assessed during the 28 days. In the diabetic group, significant weight regain upon treatment with extract was observed like that of the control group. The diabetic groups administered with the samples significantly reduced Glycated hemoglobin A1c (HbA1c) levels compared to the control group. The administration of streptozotocin increased plasma levels of total cholesterol, low-density lipoprotein (LDL), and triglycerides (TG), as well as a decrease in the level of high-density lipoprotein (HDL), when compared to the normal group. Administration of samples significantly (p < 0.05, 0.01, and 0.001, n = 8) reduced the elevated levels of serum alanine transaminase (ALT) and alkaline phosphatase (ALP). Additionally, administering of the samples significantly reduced the elevated creatinine levels, indicating improved kidney function. The activity of superoxide dismutase (SOD), an antioxidant enzyme, was significantly increased in the sample-treated groups, reaching levels comparable to the normal control group (p < 0.001, n = 8). Similar results were observed in the activity of catalase (CAT), suggesting the antioxidant and antidiabetic potentials of the plant.

    Conclusions: These findings suggested that Tr-Crd extract and its fractions could be used as an antidiabetic drug as ameliorate the alterations caused by streptozotocin injection. However, further studies in this connection are needed to evaluate its toxicological profile and isolate the responsible compounds in a pure state.

  • Article
    Khadija El Ouahdani, Imane Es-safi, Meryem Slighoua, Omkulthom Al kamaly, Anwar M. Alnakhli, Dalila Bousta
    Journal of Biological Regulators and Homeostatic Agents. 2023, 37(9): 4613-4622. https://doi.org/10.23812/j.biol.regul.homeost.agents.20233709.451
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    Background: Bacterial resistance to antibiotics and cancer cells resistance to chemotherapeutic drugs are two major public health issues. Thymus algeriensis Boiss. & Reut. and Artemisia herba-alba Asso are two common medicinal plants used to combat several pathologies, including bacterial infections and different types of cancer. This study aims to assess the cytotoxic, antibacterial and antifungal activities of each single essential oil and their combination in vitro and in silico.

    Methods: The cytotoxicity was evaluated in vitro towards three cell lines: liver human hepatocyte carcinoma cell line, metastatic adenocarcinoma Michigan Cancer Foundation-7, and Anderson-Metastatic Breast 231. Antibacterial activity was tested by the disc diffusion method on three bacterial and two fungal strains. The subacute oral toxicity was performed to assess the potential toxicity of the studied Essential Oils (EOs) followed by an analysis of the blood biochemical parameters. Lastly, docking studies were performed to assess the antimicrobial effect of Thymol, Chrysanthenone, Camphor and Borneol.

    Results: The results of the cytotoxicity test showed that there is a good dose-effect correlation between the essential oils and their mixture for the range of concentrations tested (0–50 μg/mL). However, the mixture induced a greater antiproliferative effect compared to the two oils tested separately against the three cell lines. The antibacterial and antifungal activities have revealed that the essential oil of Thymus (T.) algeriensis has an interesting antibacterial and antifungal activity against Bacillus subtilis and Penicillium digitatum with complete inhibition at 3.125 and 6.25 μg/mL, respectively. Similarly, Staphylococcus (S.) aureus had a very high sensitivity to the essential oil of Artemisia (A.) herba-alba with an inhibitory concentration of 3.125 μg/mL, as well as potent activity against Candida albicans and Penicillium digitatum, which were inhibited at 6.250 μg/mL. The subacute toxicity results showed no toxic effects in mice treated with the essential oils mixture (150 mg/kg) compared to the control group (p < 0.05). The molecular docking showed that thymol exhibited the highest activity among the molecules studied.

    Conclusions: These studies show that the essential oils of T. algeriensis and A. herba-alba have great antiproliferative power important synergistic effect, and good antibacterial and antifungal activities.