Antidiarrheal and Cardio-Depressant Effects of Himalaiella heteromalla (D.Don) Raab-Straube: In Vitro, In Vivo, and In Silico Studies
Abstract
:1. Introduction
2. Results
2.1. Phytochemical Analysis of Himalaiella heteromalla
2.2. HPLC Separation of Phenolic Acids and Flavonoids
2.3. Effect on Jejunum Preparations
2.4. Effect on Tracheal Preparations
2.5. Effect on Aortic Preparations
2.6. Effect on Atria Preparations
2.7. Antiperistalsis Activity
2.8. Antidiarrheal Activity
2.9. Anti-Inflammatory Activity
2.10. In Silico Studies
3. Discussion
4. Materials and Methods
4.1. Extract Preparation
4.2. Animal Housing
4.3. Chemicals
4.4. Qualitative Phytochemical Detection
4.5. HPLC Separation of Phenolic Acids and Flavonoids
4.6. In Vitro Experiments
4.6.1. Isolated Rabbit Jejunum Preparation
4.6.2. Isolated Rabbit Tracheal Preparations
4.6.3. Isolated Rabbit Paired Atria Preparations:
4.6.4. Isolated Rabbit Aorta Preparations
4.7. In Vivo Activities
4.7.1. Antiperistalsis Activity
4.7.2. Antidiarrheal Activity
4.7.3. Carrageenan-Induced Rat’s Hind Paw Edema Method
4.8. In Silico Studies
4.9. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Saklani, A.; Hegde, B.; Mishra, P.; Singh, R.; Mendon, M.; Chakrabarty, D.; Kamath, D.V.; Lobo, A.; Mishra, P.D.; Dagia, N.M.; et al. NF-κB dependent anti-inflammatory activity of chlorojanerin isolated from Saussurea heteromalla. Phytomedicine 2012, 19, 988–997. [Google Scholar] [CrossRef] [PubMed]
- Sajad, M.A.; Khan, M.S.; Bahadur, S.; Shuaib, M.; Naeem, A.; Zaman, W.; Ali, H. Nickel phytoremediation potential of some plant species of the Lower Dir, Khyber Pakhtunkhwa, Pakistan. Limnol. Rev. 2020, 20, 13–22. [Google Scholar] [CrossRef]
- Khatun, S. Antimicrobial activity of tuber extracts of the medicinal plant coleus forskohlii. Plant Cell Biotechnol. Mol. Biol. 2020, 21, 11–17. [Google Scholar]
- Gao, Q.; Yang, M.; Zuo, Z. Overview of the anti-inflammatory effects, pharmacokinetic properties and clinical efficacies of arctigenin and arctiin from Arctium lappa L. Acta Pharmacol. Sin. 2018, 39, 787–801. [Google Scholar] [CrossRef]
- Kang, H.S.; Lee, J.Y.; Kim, C.J. Anti-inflammatory activity of arctigenin from Forsythiae Fructus. J. Ethnopharmacol. 2008, 116, 305–312. [Google Scholar] [CrossRef]
- Hayashi, K.; Narutaki, K.; Nagaoka, Y.; Hayashi, T.; Uesato, S. Therapeutic effect of arctiin and arctigenin in immunocompetent and immunocompromised mice infected with influenza A virus. Biol. Pharm. Bull. 2010, 33, 1199–1205. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cheng, X.; Zhong, F.; He, K.; Sun, S.; Chen, H.; Zhou, J. EHHM, a novel phenolic natural product from Livistona chinensis, induces autophagy-related apoptosis in hepatocellular carcinoma cells. Oncol. Lett. 2016, 12, 3739–3748. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rathore, S.; Tiwari, J.K.; Malik, Z.A. Ethnomedicinal survey of herbaceous flora traditionally used in health care practices by inhabitants of dhundsir gad watershed of garhwal himalaya, india. Glob. J. Res. Med. Plants Indig. Med. 2015, 4, 65–78. [Google Scholar]
- Khare, C.P. (Ed.) Indian Medicinal Plants; Springer: New York, NY, USA, 2007; ISBN 978-0-387-70637-5. [Google Scholar]
- Kala, C.P. Medicinal plants of the high altitude cold desert in India: Diversity, distribution and traditional uses. Int. J. Biodivers. Sci. Manag. 2006, 2, 43–56. [Google Scholar] [CrossRef]
- Singh, A.; Lal, M.; Samant, S.S. Diversity, indigenous uses and conservation prioritization of medicinal plants in lahaul valley, proposed cold desert biosphere reserve, India. Int. J. Biodivers. Sci. Manag. 2009, 5, 132–154. [Google Scholar] [CrossRef] [Green Version]
- Wahid, M.; Saqib, F.; Ahmedah, H.T.; Gavris, C.M.; De Feo, V.; Hogea, M.; Moga, M.; Chicea, R. Cucumis sativus L. Seeds Ameliorate Muscular Spasm-Induced Gastrointestinal and Respiratory Disorders by Simultaneously Inhibiting Calcium Mediated Signaling Pathway. Pharmaceuticals 2021, 14, 1197. [Google Scholar] [CrossRef] [PubMed]
- Sirous, H.; Chemi, G.; Campiani, G.; Brogi, S. An integrated in silico screening strategy for identifying promising disruptors of p53-MDM2 interaction. Comput. Biol. Chem. 2019, 83, 107105. [Google Scholar] [CrossRef]
- Kuhn, B.; Kollman, P.A. Binding of a diverse set of ligands to avidin and streptavidin: An accurate quantitative prediction of their relative affinities by a combination of molecular mechanics and continuum solvent models. J. Med. Chem. 2000, 43, 3786–3791. [Google Scholar] [CrossRef]
- Gilani, A.U.H.; Shah, A.J.; Yaeesh, S. Presence of cholinergic and calcium antagonist constituents in Saussurea lappa explains its use in constipation and spasm. Phyther. Res. 2007, 21, 541–544. [Google Scholar] [CrossRef]
- Chen, J.C.; Ho, T.Y.; Chang, Y.S.; Wu, S.L.; Hsiang, C.Y. Anti-diarrheal effect of Galla Chinensis on the Escherichia coli heat-labile enterotoxin and ganglioside interaction. J. Ethnopharmacol. 2006, 103, 385–391. [Google Scholar] [CrossRef] [PubMed]
- Cheng, Y.; Li, X.; Tse, H.F.; Rong, J. Gallic acid-L-leucine conjugate protects mice against LPS-induced inflammation and sepsis via correcting proinflammatory lipid mediator profiles and oxidative stress. Oxid. Med. Cell. Longev. 2018, 2018, 1081287. [Google Scholar] [CrossRef]
- Gilani, A.H.; Ghayur, M.N.; Saify, Z.S.; Ahmed, S.P.; Choudhary, M.I.; Khalid, A. Presence of cholinomimetic and acetylcholinesterase inhibitory constituents in betel nut. Life Sci. 2004, 75, 2377–2389. [Google Scholar] [CrossRef] [PubMed]
- Lanuzza, F.; Occhiuto, F.; Monforte, M.T.; Tripodo, M.M.; D’Angelo, V.; Galati, E.M. Antioxidant phytochemicals of Opuntia ficus-indica (L.) Mill. cladodes with potential anti-spasmodic activity. Pharmacogn. Mag. 2017, 13, S424–S429. [Google Scholar] [CrossRef]
- Ghayur, M.N.; Khan, H.; Gilani, A.H. Antispasmodic, bronchodilator and vasodilator activities of (+)-catechin, a naturally occurring flavonoid. Arch. Pharm. Res. 2007, 30, 970–975. [Google Scholar] [CrossRef]
- Zhang, M.; Zhao, C.; Shao, Q.; Yang, Z.; Zhang, X.; Xu, X.; Hassan, M. Determination of water content in corn stover silage using near-infrared spectroscopy. Int. J. Agric. Biol. Eng. 2019, 12, 143–148. [Google Scholar] [CrossRef]
- Saqib, F.; Janbaz, K.H. Rationalizing ethnopharmacological uses of Alternanthera sessilis: A folk medicinal plant of Pakistan to manage diarrhea, asthma and hypertension. J. Ethnopharmacol. 2016, 182, 110–121. [Google Scholar] [CrossRef] [PubMed]
- Karaki, H.; Ozaki, H.; Hori, M.; Mitsui-Saito, M.; Amano, K.I.; Harada, K.I.; Miyamoto, S.; Nakazawa, H.; Won, K.J.; Sato, K. Calcium movements, distribution, and functions in smooth muscle. Pharmacol. Rev. 1997, 49, 157–230. [Google Scholar] [PubMed]
- Bolton, T.B. Mechanisms of action of transmitters and other substances on smooth muscle. Physiol. Rev. 1979, 59, 606–718. [Google Scholar] [CrossRef]
- Fleckenstein, A. Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Annu. Rev. Pharmacol. Toxicol. 1977, 17, 149–166. [Google Scholar] [CrossRef]
- Yakubu, M.T.; Salimon, S.S. Antidiarrhoeal activity of aqueous extract of Mangifera indica L. leaves in female albino rats. J. Ethnopharmacol. 2015, 163, 135–141. [Google Scholar] [CrossRef] [PubMed]
- Janbaz, K.H.; Jan, A.; Qadir, M.I.; Gilani, A.H. Spasmolytic, bronchodilator and vasorelaxant activity of methanolic extract of tephrosia purpurea. Acta Pol. Pharm.-Drug Res. 2013, 70, 261–269. [Google Scholar]
- Janbaz, K.H.; Arif, J.; Saqib, F.; Imran, I.; Ashraf, M.; Zia-Ul-Haq, M.; Jaafar, H.Z.E.; De Feo, V. In-vitro and in-vivo validation of ethnopharmacological uses of methanol extract of Isodon rugosus Wall. ex Benth. (Lamiaceae). BMC Complement. Altern. Med. 2014, 14, 71. [Google Scholar] [CrossRef] [Green Version]
- Janbaz, K.H.; Nisa, M.; Saqib, F.; Imran, I.; Zia-Ul-Haq, M.; De Feo, V. Bronchodilator, vasodilator and spasmolytic activities of methanolic extract of Myrtus communis L. J. Physiol. Pharmacol. 2013, 64, 479–484. [Google Scholar]
- Ghayura, M.N.; Gilani, A.H. A-Adrenergic Receptor Mediated Hypertensive and Vasoconstrictor Effects of Dietary Radish Leaves Extract. J. Health Sci. 2007, 53, 151–155. [Google Scholar] [CrossRef] [Green Version]
- Gilani, A.H.; Jabeen, Q.; Ghayur, M.N.; Janbaz, K.H.; Akhtar, M.S. Studies on the antihypertensive, antispasmodic, bronchodilator and hepatoprotective activities of the Carum copticum seed extract. J. Ethnopharmacol. 2005, 98, 127–135. [Google Scholar] [CrossRef]
- Deliorman Orhan, D.; Hartevioǧlu, A.; Küpeli, E.; Yesilada, E. In vivo anti-inflammatory and antinociceptive activity of the crude extract and fractions from Rosa canina L. fruits. J. Ethnopharmacol. 2007, 112, 394–400. [Google Scholar] [CrossRef]
- Zhao, C.; Cao, Y.; Ma, Z.; Shao, Q. Optimization of liquid ammonia pretreatment conditions for maximizing sugar release from giant reed (Arundo donax L.). Biomass Bioenergy 2017, 98, 61–69. [Google Scholar] [CrossRef]
- Qiao, X.; Zhao, C.; Shao, Q.; Hassan, M. Structural Characterization of Corn Stover Lignin after Hydrogen Peroxide Presoaking Prior to Ammonia Fiber Expansion Pretreatment. Energy Fuels 2018, 32, 6022–6030. [Google Scholar] [CrossRef]
- Chen, D.; Cen, K.; Cao, X.; Chen, F.; Zhang, J.; Zhou, J. Insight into a new phenolic-leaching pretreatment on bamboo pyrolysis: Release characteristics of pyrolytic volatiles, upgradation of three phase products, migration of elements, and energy yield. Renew. Sustain. Energy Rev. 2021, 136, 110444. [Google Scholar] [CrossRef]
- Chen, D.; Cen, K.; Cao, X.; Zhang, J.; Chen, F.; Zhou, J. Upgrading of bio-oil via solar pyrolysis of the biomass pretreated with aqueous phase bio-oil washing, solar drying, and solar torrefaction. Bioresour. Technol. 2020, 305, 123130. [Google Scholar] [CrossRef] [PubMed]
- Chen, D.; Chen, F.; Cen, K.; Cao, X.; Zhang, J.; Zhou, J. Upgrading rice husk via oxidative torrefaction: Characterization of solid, liquid, gaseous products and a comparison with non-oxidative torrefaction. Fuel 2020, 275, 117936. [Google Scholar] [CrossRef]
- Chen, D.; Cen, K.; Chen, F.; Ma, Z.; Zhou, J.; Li, M. Are the typical organic components in biomass pyrolyzed bio-oil available for leaching of alkali and alkaline earth metallic species (AAEMs) from biomass? Fuel 2020, 260, 116347. [Google Scholar] [CrossRef]
- VAN ROSSUM, J.M. Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch. Int. Pharmacodyn. Thér. 1963, 143, 299–330. [Google Scholar] [PubMed]
- Zarei, M.; Mohammadi, S.; Komaki, A. Antinociceptive activity of Inula britannica L. and patuletin: In vivo and possible mechanisms studies. J. Ethnopharmacol. 2018, 219, 351–358. [Google Scholar] [CrossRef]
Sr.No. | Compound | Retention Time (min) | Concentration (µg/g) |
---|---|---|---|
1. | Gallic Acid | 2.7 | 184.98 |
2. | Catechin | 3.3 | 160.37 |
3. | HB acid | 6.8 | 22.80 |
4. | Vanilic acid | 8.1 | 9.08 |
Name(PubChem ID) | Docking Score | ∆GBinding | Log Ki (µMolar) | ∆GCoulomb | ∆GCovalent | ∆GHbond | ∆GLipophilic | ∆GSolv GB | ∆GvdW | Residue-Ligand Interactions with Distance (Å) | |
---|---|---|---|---|---|---|---|---|---|---|---|
Hydrogen Bonds | Hydrophobic Bonds | ||||||||||
Arctiin (100528) | −11.63 | −60.79 | −23.17 | −16.29 | 10.56 | −1.22 | −42.47 | 47.40 | −55.32 | Asn513 (2.46), Leu225 (1.77), C-H Bond: Thr231 (2.58), Tyr529 (2.99), π-Donor Hydrogen Bond: Trp525 (2.71), Trp525 (2.66) | π-Sulfur Bond: Cys532 (5.42), π-π Stacked Bond: Trp503 (4.56), π-π T shaped Bond: Tyr148 (5.21), Alkyl Bond: Ile222 (4.69), Leu225 (4.41), Cys532 (3.20), π-Alkyl Bond: Tyr148 (3.64), Tyr506 (3.99), Tyr529 (4.91), Tyr529 (3.98), Leu225 (4.98) |
Arctigenin (64981) | −9.72 | −46.56 | −16.99 | −16.92 | 6.57 | −0.68 | −30.61 | 31.10 | −34.45 | Ala238 (1.64) C-H Bond: Thr234 (3.03), Ile222 (2.77), Leu225 (2.77), Leu225 (2.65), Tyr148 (2.40) | π-π T shaped Bond: Trp503 (5.58), Trp525 (5.37), π-Alkyl Bond: Tyr148 (4.40), Trp199 (4.19), Trp199 (4.18), Phe221 (4.72), Trp525 (3.99), Trp525 (4.05), Leu225 (5.49), Ala238 (4.30) |
Catechin (9064) | −7.59 | −52.22 | −19.45 | −29.22 | 2.89 | −2.92 | −13.93 | 27.23 | −34.12 | Tyr148 (2.05), Ile222 (2.39), Ile222 (3.03), Ser226 (1.92), Ser226 (1.80) | π-π T shaped Bond: Tyr506 (5.74) |
Chlorojanerin (182408) | −7.13 | −43.68 | −15.74 | −20.79 | 2.92 | −1.98 | −19.31 | 33.51 | −38.02 | Tyr127 (1.87), Tyr148 (2.30), Asn513 (3.02) Asn513 (3.03), Asn526 (2.03), Ser226 (2.60), C-H Bond: Leu225 (2.63), Leu225 (2.55), Ser226 (2.55) | Alkyl Bond: Lys522 (5.21), Lys522 (5.47), π-Alkyl Bond: Phe124 (4.85), Trp525 (4.93), Trp525 (5.15), Trp525 (3.59), Trp525 (4.43) |
Cynaropicrin (119093) | −6.76 | −48.69 | −17.92 | −19.54 | 1.54 | −1.63 | −18.37 | 26.11 | −36.81 | Tyr148 (3.00), Ile222 (2.49), Asn526 (1.77), Leu225 (1.92), Thr231 (2.64) | Alkyl Bond: Lys522 (5.30), π-Alkyl Bond: Phe124 (5.48), Tyr127 (4.81), Trp525 (3.49), Trp525 (4.36) |
Cyclooxygenase-2 (COX-2, PDB ID:5IKQ) | |||||||||||
Arctiin (100528) | −8.49 | −41.01 | −14.58 | −21.01 | 10.60 | −2.56 | −23.77 | 33.40 | −36.96 | Lys83 (1.88), Ser12 (3.00), Ser120 (1.73), Pro84 (1.67), C-H Bond: Ser120 (2.66) | π-π T shaped Bond: Tyr11 (5.32), Alkyl Bond: Ala112 (3.50), Val89 (4.95), Leu93 (4.90), Val117 (4.37), Leu109 (4.79), Ile113 (5.11), π-Alkyl Bond: Tyr116 (4.01), Val89 (3.76), Le113 (4.71) |
Arctigenin (64981) | −7.37 | −27.91 | −8.89 | −5.55 | 18.02 | 0.00 | −31.09 | 26.83 | −35.44 | C-H Bond: Ala528 (2.91), Ser120 (2.62), Ser531 (2.79) | π-σ Bond: Val117 (2.48), Alkyl Bond: Arg121 (4.83), Val350 (4.80), Leu353 (5.46), Val89 (4.59), Leu93 (5.01), π-Alkyl Bond: Val350 (5.15), Leu353 (4.99), Val524 (4.56) Ala528 (4.24) |
Cynaropicrin (119093) | −4.28 | −35.97 | −12.39 | −11.96 | 3.10 | −1.10 | −18.58 | 17.86 | −25.30 | Arg121(1.81), Arg121 (2.46), C-H Bond: Val117 (2.51) | Alkyl Bond: Pro84 (5.14), Val89 (5.04), Val89 (4.09), Pro84 (4.81), Val89 (4.45), Ile92 (5.00), Leu93 (3.76), π-Alkyl Bond: Tyr116 (5.22) |
Catechin (9064) | −2.84 | −11.87 | −1.93 | 2.05 | 4.15 | −0.61 | −11.82 | 15.82 | −18.71 | Arg121 (2.76), Tyr116 (2.79), C-H Bond: Pro84 (2.55), Tyr116 (2.29) | π-π T shaped Bond: Tyr116 (5.65), Tyr116 (4.80), Alkyl Bond: Val89 (4.00), π-Alkyl Bond: Tyr116 (5.27), Val89 (4.80), Pro84 (5.20) |
Lipoxygenase 5 (LOX-5, PDB ID: 6N2W) | |||||||||||
Arctiin (100528) | −5.76 | −30.76 | −10.13 | −14.19 | 6.04 | −2.11 | −16.17 | 44.56 | −46.53 | His372 (2.55), Glu417 (1.89), C-H Bond: Glu417 (3.00), Gln413 (2.62) | Electrostatic π-Anion Bond: Ile673 (4.46) π-π Stacked Bond: His372 (4.40), Alkyl Bond: Ala410 (3.62), Leu368 (4.59), Leu368 (4.40), π-Alkyl Bond: His367 (3.52), His372 (4.83), His372 (3.83), Ile406 (5.49), Ala410 (4.09) |
Catechin (9064) | −4.95 | −30.81 | −10.15 | −22.76 | 5.66 | −2.38 | −15.10 | 39.78 | −32.68 | Arg596 (2.34), His600 (1.80), π-Donor Hydrogen Bond: His372 (3.10) | π-π Stacked Bond: His367 (4.84), π-π T shaped Bond: His372 (5.54), Trp599 (5.02), Alkyl Bond: Leu607 (5.03), π-Alkyl Bond: Leu607 (5.21), Ala603 (4.88) |
Arctigenin (64981) | −4.84 | −42.94 | −15.42 | −28.08 | 3.66 | −3.06 | −18.99 | 34.43 | −29.61 | Arg596 (2.57), Arg596 (1.88), His600 (1.82) | Electrostatic π-Cation Bond: Arg596 (3.17), Alkyl Bond: Ala410 (3.75), Ala426 (3.63), π-Alkyl Bond: His367 (4.32), Trp599 (4.00), Leu607 (5.10), Ala426 (3.91) |
Cynaropicrin (119093) | −3.45 | −14.54 | −3.09 | −13.54 | 2.95 | −0.81 | −17.02 | 46.96 | −33.09 | His367 (2.76), Ile673 (1.84), C-H Bond: Ala410 (2.98) | Alkyl Bond: Ala603 (4.92), Ala603 (3.87), Leu607, (5.09), Leu607 (4.33) |
Chlorojanerin (182408) | −3.30 | −32.60 | −10.93 | −3.30 | 0.38 | −0.62 | −13.65 | 19.69 | −35.10 | Thr427 (2.78), Arg596 (1.77), His600 (2.15), C-H Bond: His367 (2.97), His600 (2.56), Pro569 (2.73) | π-π T shaped Bond: Trp599 (5.64), Alkyl Bond: Ala603 (3.39), Val604 (4.44), π-Alkyl Bond: His360 (5.21), His432 (4.65), Trp599 (4.91) His600 (4.18) |
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Saqib, F.; Usman, F.; Malik, S.; Bano, N.; Ur-Rahman, N.; Riaz, M.; Marc, R.A.; Mureşan, C.C. Antidiarrheal and Cardio-Depressant Effects of Himalaiella heteromalla (D.Don) Raab-Straube: In Vitro, In Vivo, and In Silico Studies. Plants 2022, 11, 78. https://0-doi-org.brum.beds.ac.uk/10.3390/plants11010078
Saqib F, Usman F, Malik S, Bano N, Ur-Rahman N, Riaz M, Marc RA, Mureşan CC. Antidiarrheal and Cardio-Depressant Effects of Himalaiella heteromalla (D.Don) Raab-Straube: In Vitro, In Vivo, and In Silico Studies. Plants. 2022; 11(1):78. https://0-doi-org.brum.beds.ac.uk/10.3390/plants11010078
Chicago/Turabian StyleSaqib, Fatima, Faisal Usman, Shehneela Malik, Naheed Bano, Najm Ur-Rahman, Muhammad Riaz, Romina Alina Marc (Vlaic), and Crina Carmen Mureşan. 2022. "Antidiarrheal and Cardio-Depressant Effects of Himalaiella heteromalla (D.Don) Raab-Straube: In Vitro, In Vivo, and In Silico Studies" Plants 11, no. 1: 78. https://0-doi-org.brum.beds.ac.uk/10.3390/plants11010078