<p>Bioactive Compounds from <em>Abelmoschus manihot L</em>. Alleviate the Progression of Multiple Myeloma in Mouse Model and Improve Bone Marrow Microenvironment</p>

Abstract

Abelmoschus manihot (L.) Medik. (Malvaceae) derived Huangkui capsules (HKC) represent a traditional Chinese medicine that has been widely applied to the clinical therapy of kidney and inflammatory diseases. The present study aimed to determine the potential therapeutic effects and underlying mechanisms of the ingredients on Multiple Myeloma (MM), an incurable disease that exhibits malignant plasma cell clonal expansion in the bone marrow. Methods: A 5TMM3VT syngeneic MM-prone model was established and treated with HKC. Murine pre-osteoblast MC3T3-E1 and pre-osteoclast Raw264.7 cells were treated with nine flavonoid compounds extracted from the flowers of Abelmoschus manihot. MC3T3-E1 and Raw264.7 cells were then examined by alizarin red staining and tartrate-resistant acid phosphatase activity staining, respectively. The proliferation of two human MM cells (ARP1, H929) was examined by performing an MTT assay following treatment with flavonoid compounds. Additionally, the cell cycle was analyzed via staining and flow cytometry. The differential expressions of certain proteins were detected via Western blotting, transcriptomic RNA-sequencing as well as RT-qPCR. Results: The results revealed that MM-prone animals appeared to be protected following HKC treatment, as evidenced by a prolonged survival rate. Furthermore, four of the nine flavonoid compounds [Hyperin/Hyperoside, HK-2; Cannabiscitrin, HK-3; 3-O-kaempferol-3-O-acetyl-6-O-(p-coumaroyl)-β-D-glucopyranoside, HK-11; 8-(2''-pyrrolidione-5''-yl)quercetin, HK-B10] induced the differentiation of murine pre-osteoblast MC3T3-E1 cells. In addition, two compounds [Isomyricitrin, HK-8; quercetin-8-(2''-pyrrolidione-5"-yl)-3ʹ-O-β-D-glucopyranosid, HK-E3] suppressed osteoclastogenesis in murine Raw264.7 cells. HK-11 directly inhibited MM cells (ARP1 and H929) proliferation and induced G0/G1 cell cycle arrest, which may have involved the suppressing β-catenin protein, increasing expressions of IL-6 and TNF-α, as well as activating mature TGF-β1 and some other metabolic pathways. Conclusion: These results of the present study indicated that the bio-active ingredients of HKC exerted protective effects on MM mouse survival through promoting osteoblastogenesis and suppressing osteoclastogenesis, thus improving the bone marrow microenvironment to inhibit MM cell proliferation.

Traditional Uses, Chemical Constituents, Biological Properties, Clinical Settings, and Toxicities of Abelmoschus manihot L.: A Comprehensive Review

“…However, more evidence is needed to obtain detailed structural information as well as the mechanism of action of AMPS-a and explore it as a potential antitumor agent. In a recent study, Hou et al. (2020) found that HKC, at 3.75 g/kg/day, prominently prolonged the survival rate of a multiple myeloma-prone mouse model.…”

“…Further phytochemical investigations proved that four bioactive ingredients from HKC, namely hyperoside (28), cannabiscitrin (29), 8-(2′′-pyrrolidione-5-yl)-quercetin (48), and 3- O -kaempferol-3- O -acetyl-6- O -(p-coumaroyl)-β-D-glucopyranoside (49), at concentrations of 0.05 and 5 μM, notably promoted the differentiation of murine pre-osteoblast MC3T3-E1 cells ( Hou et al., 2020 ). Furthermore, compound (49) suppressed the proliferation of multiple myeloma ARP1 and H929 cells and induced cell cycle arrest at G 0 /G 1 phase, which may be related to inhibition of the β-catenin protein, upregulation of the expressions of IL-6 and TNF-α, as well as activation of mature TGF-β1 ( Hou et al., 2020 ). The results from this study indicated that HKC exerts protective effects and may serve as a promising anti-multiple myeloma drug.…”

“…For hundreds of years, A. manihot has been widely used as a folk medicine in clinical practice in China to cure forms of chronic kidney disease (CKD) and exerts significant effects by decreasing the protein content in urine and protecting kidney function ( Peng et al., 2010 ; Wang and Gao, 2010 ; Zhu and Bi, 2010 ; Tsumbu et al., 2012 ). According to the Compendium of Materia Medica , a famous classical book of Chinese materia medica compiled by Shizhen Li (1518–1593 CE), the flowers of A. manihot have been recorded as an effective herb to treat malignant sores, cellulitis, and burns ( Jiang et al., 2012 ; Cai et al., 2017a ; Hou et al., 2020 ). Importantly, A. manihot flowers are listed in the 2015 edition of the Pharmacopoeia of the People’s Republic of China (a.k.a.…”

Efficacy and safety of Huangkui capsule for diabetic nephropathy

“…[ 10 ] Huangkui capsule has applied to treat DN for about 10 years in clinical practice with no reported adverse reactions. [ 11 , 12 ]…”

Acupuncture Synergized With Bortezomib Improves Survival of Multiple Myeloma Mice via Decreasing Metabolic Ornithine

“…The latest clinical MM therapy is a new immunomodulatory therapy using chimeric antigen receptor T cells, bispecific T cell conjugates, and immune checkpoint inhibitors (6). Although the therapeutic armamentarium for MM has continued to evolve (7)(8)(9)(10)(11)(12)(13)(14), MM still possesses the characteristics of high relapse and incurability. It is necessary to explore more effective therapies to improve MM prognosis significantly.…”