Research Article Phytotherapeutic Approach in the Management of Cisplatin Induced Vomiting; Neurochemical Considerations in Pigeon Vomit Model Ihsan Ullah , 1 Fazal Subhan , 2 Muhammad Shahid, 2 Nisar Ahmad, 3,4 Rehmat Shah, 5 Javaid Alam , 6 Ikram Ul Haq , 7 Rahim Ullah , 8 Muhammad Ayaz , 9 and H. C. Ananda Murthy 10,11 1 Department of Pharmacy, University of Swabi, Swabi, Pakistan 2 Department of Pharmacy, Institute of Integrative Biosciences, CECOS University of IT and Emerging Sciences, Peshawar, KP, Pakistan 3 Department of Pharmacy, University of Peshawar, Peshawar, Pakistan 4 Department of Pharmacy, Islamia College of Pharmacy, Sialkot, Pakistan 5 Pharmacist, Health Department, Khyber Pakhtunkhwa, Pakistan 6 Drug and Herbal Research Center, Faculty of Pharmacy, University Kebangsan, Malaysia 7 National Institute of Health, Islamabad, Pakistan 8 Sarhad University of Science and Information Technology, Peshawar, Pakistan 9 Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara, 18000 Dir (L), KP, Pakistan 10 Department of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, P O Box 1888, Adama, Ethiopia 11 Department of Prosthodontics, Saveetha Dental College & Hospital, Saveetha Institute of Medical and Technical Science (SIMATS), Saveetha University, Chennai 600 077, Tamil Nadu, India Correspondence should be addressed to Ihsan Ullah; ihsanmkd@gmail.com, Muhammad Ayaz; ayazuop@gmail.com, and H. C. Ananda Murthy; anandkps350@gmail.com Received 11 July 2022; Revised 29 August 2022; Accepted 2 September 2022; Published 13 September 2022 Academic Editor: Tarique Hussain Copyright © 2022 Ihsan Ullah et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cisplatin induced vomiting involves multiple mechanisms in its genesis and a single antiemetic agent do not cover both the phases (acute & delayed) of vomiting in clinics; necessitating the use of antiemetics in combination. Cannabis sativa and other selected plants have ethnopharmacological significance in relieving emesis. The aim of the present study was to investigate the intrinsic antiemetic profile of Cannabis sativa (CS), Bacopa monniera (BM, family Scrophulariaceae), and Zingiber officinale (ZO, family Zingiberaceae) in combinations against vomiting induced by highly emetogenic anticancer drug-cisplatin in pigeons. We have analysed the neurotransmitters which trigger the vomiting response centrally and peripherally. Electrochemical detector (ECD) was used for the quantification of neurotransmitters and their respective metabolites by high performance liquid chromatography in the brain stem (BS) and area postrema (AP) while peripherally in the small intestine. Cisplatin (7 mg/kg i.v.) induced reliable vomiting throughout the observation period (24 hrs). CS-HexFr (10 mg) + BM-MetFr (10 mg)–Combination 1, BM-ButFr (5 mg) + ZO-ActFr (25 mg)–Combination 2, ZO-ActFr (25 mg) + CS-HexFr (10 mg)–Combination 3, and CS-HexFr (10 mg) + BM-ButFr (5 mg)– Combination 4; provided ~30% (30 ± 1:1), 70% (12 ± 0:4; P <0:01), 60% (19 ± 0:2; P <0:05) and 90% (05 ± 0:1; P <0:001) protection, respectively, against cisplatin induced vomiting as compared to cisplatin control. Standard MCP (30 mg) provided ~50% (23 ± 0:3) protection (P >0:05). CS Hexane fraction (10 mg/kg), BM methanolic (10 mg/kg) and bacoside rich n-butanol fraction (5 mg/kg) and ZO acetone fraction (25 mg/kg) alone provided ~62%, 36%, 71%, and 44% protection, respectively, as compared to cisplatin control. The most effective and synergistic combination 4 was found to reduce 5HT and 5HIAA (P<0:05 – 0:001) in all the brain areas area postrema (AP)+brain stem (BS) and intestine at the 3 rd hour of cisplatin administration. In continuation, at the Hindawi Oxidative Medicine and Cellular Longevity Volume 2022, Article ID 3914408, 13 pages https://doi.org/10.1155/2022/3914408