Journal of Ethnopharmacology xxx (xxxx) xxx Please cite this article as: Yusha’u Shu’aibu Baraya, Journal of Ethnopharmacology, https://doi.org/10.1016/j.jep.2020.113522 Available online 28 October 2020 0378-8741/© 2020 Elsevier B.V. All rights reserved. Strobilanthes crispus bioactive subfraction inhibits tumor progression and improves hematological and morphological parameters in mouse mammary carcinoma model Yusha’u Shu’aibu Baraya a , Hassan Muhammad Yankuzo b , Kah Keng Wong c , Nik Soriani Yaacob d, * a Department of Veterinary Pathology, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, Sokoto, Nigeria b Department of Medical Biochemistry, Faculty of Basic Medical Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria c Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kelantan, Malaysia d Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kelantan, Malaysia A R T I C L E INFO Keywords: Strobilanthes crispus Lutein β-sitosterol Breast cancer Antitumor Antimetastasis 4T1 mammary Carcinoma Tumor induction Medicinal plant ABSTRACT Ethnopharmacological relevance: Locally known as ‘pecah batu’, ‘bayam karang’, ‘keci beling’ or ‘batu jin’, the Malaysian medicinal herb, Strobilanthes crispus (S. crispus), is traditionally used by the local communities as alternative or adjuvant remedy for cancer and other ailments and to boost the immune system. S. crispus has demonstrated multiple anticancer therapeutic potential in vitro and in vivo. A pharmacologically active fraction of S. crispus has been identifed and termed as F3. Major constituents profled in F3 include lutein and β-sitosterol. Aim of the study: In this study, the effects of F3, lutein and β-sitosterol on tumor development and metastasis were investigated in 4T1-induced mouse mammary carcinoma model. Materials and methods: Tumor-bearing mice were fed with F3 (100 mg/kg/day), lutein (50 mg/kg/day) and β-sitosterol (50 mg/kg/day) for 30 days (n = 5 each group). Tumor physical growth parameters, animal body weight and development of secondary tumors were investigated. The safety profle of F3 was assessed using hematological and histomorphological changes on the major organs in normal control mice (NM). Results: Our fndings revealed signifcant reduction of physical tumor growth parameters in all tumor-bearing mice treated with F3 (TM-F3), lutein (TM-L) or β-sitosterol (TM-β) as compared with the untreated group (TM). Statistically signifcant reduction in body weight was observed in TM compared to the NM or treated (TM- F3, TM-L and TM-β) groups. Histomorphological examination of tissue sections from the F3-treated group showed normal features of the vital organs (i.e., liver, kidneys, lungs and spleen) which were similar to those of NM. Administration of F3 to NM mice (NM-F3) did not cause signifcant changes in full blood count values. Conclusion: F3 signifcantly reduced the total tumor burden and prevented secondary tumor development in metastatic breast cancer without signifcant toxicities in 4T1-induced mouse mammary carcinoma model. The current study provides further support for therapeutic development of F3 with further pharmacokinetics studies. 1. Introduction Breast cancer is the most common cause of cancer-related deaths among women worldwide (Torre et al., 2015). Breast cancer metastasis is responsible for more than 90% of the human breast cancer-related deaths, and is considered the leading cause of cancer treatment failure Abbreviations: FBC, full blood count; IQR, interquartile range; NM, normal control mice; NM-F3, normal control mice treated with F3; PCV, packed cell volume; RBC, red blood cell; TM, tumor-bearing mice; TM-F3, tumor-bearing mice treated with F3; TM-L, tumor-bearing mice treated with lutein; TM-β, tumor-bearing mice treated with β-sitosterol; WBC, white blood cell. * Corresponding author. Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia. E-mail addresses: ysbgobir123@yahoo.com (Y.S. Baraya), hyankuzo@yahoo.com (H.M. Yankuzo), kahkeng@usm.my (K.K. Wong), niksoriani@usm.my, sorianiyaacob@gmail.com (N.S. Yaacob). Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm https://doi.org/10.1016/j.jep.2020.113522 Received 11 September 2020; Received in revised form 23 October 2020; Accepted 25 October 2020