Research Article In Vitro and Randomized, Double-Blind, Placebo-Controlled TrialtoDeterminetheEfficacyandSafetyofNineAntiacne Medicinal Plants OmarSaid , 1 IyadKhamaysi , 2 Abdalsalam Kmail, 3 Stephen Fulder, 1 Basheer AboFarekh, 4 RiyadAmin, 1 JamilaDaraghmeh, 3 andBasharSaad 3,4 1 Independent Researcher, Beleaf Pharma, P.O. Box 2205, Kfar Kana, Galilee 16930, Israel 2 Faculty of Medicine, Technion-ITT, Rambam Medical Center, Haifa, Israel 3 Faculty of Arts and Sciences, Arab American University Jenin, P.O. Box 240, Jenin, State of Palestine 4 Qasemi Research Center-Al-Qasemi Academy, P.O. Box 124, Baqa El-Gharbia 30100, Israel Correspondence should be addressed to Omar Said; omar@beleafherbal.com and Bashar Saad; bashar.saad@aaup.edu Received 28 February 2020; Revised 26 April 2020; Accepted 20 May 2020; Published 9 July 2020 Guest Editor: Xiangguo Shi Copyright©2020OmarSaidetal.isisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. e present in vitro and randomized, double-blind, placebo-controlled trial aims to determine the efficacy and safety of nine Mediterranean antiacne medicinal plants. e antimicrobial, antisebum, and anti-inflammatory activities of the plant extracts were evaluated in cells from the immortalized human keratinocytes (HaCaT) and human monocytic cell line (THP-1) as well as in a double-blind, randomized, and placebo-controlled trial. Most of the extracts showed no significant cytotoxic effects on HaCaT cells up to 250 μg/ml. Inula helenium (IH) and Saponaria officinalis (SO) inhibited sebum production at 90 μg/ml and 30 μg/ml, respectively. e inhibition effect of SO on the growth of Cutibacterium acnes was 1.2 times higher than that of chloramphenicol. IH and SO extracts significantly inhibited the lipopolysaccharide- (LPS-) induced IL-6 and TNF-α production in THP-1 cells reaching the control levels of untreated cells at a concentration of 250 μg/ml. SO, IH, and Solanum nigrum (SN) extracts inhibited the nitric oxide (NO) production in a dose-dependent manner. Based on these results, an antiacne herbal cream (AHC) was prepared from different portions of extracts from SO, IH, and SN, and its efficacy was evaluated in a double-blind, randomized, and controlled efficacy study with 41 acne patients, ages 18–24, who were asked to apply AHC (n � 27) or a placebo (n � 14) two to three times daily for six weeks. Results obtained indicate that the AHC has unique synergistic effects that halt sebum production, combined with highly antiseptic and anti-inflammatory activity, in which 54.95% (t � 19.37 P < 0.001) of acne inflammatory and noninflammatory lesions disappeared after two weeks, 85.3%, after five weeks (t � 14.19 P < 0.001), and 91.4%, at the end of the sixth week of application (t � 5.7 P < 0.001). In conclusion, SO, IH, and SN as single extracts and in combination as AHC showed significant antimicrobial, antisebum, and anti-inflammatory activities in vitro and in a double-blind, randomized, and controlled antiacne efficacy. erefore, AHC represents an interesting alternative treatment for acne. 1.Introduction Acne, also known as acne vulgaris, is a chronic inflammatory disease, predominantly affecting teenagers and young adults. e currently used acne treatments target its pathogenetic mechanisms. ese include keratinocyte hyperproliferation, seborrhea, colonization of follicular ducts by Cutibacterium acnes (C. acnes), and local inflammation [1–3]. Depending on the extent and severity of the lesions, therapies vary from topical applications of antibacterial, comedolytic, and sebostatic medications, to systemic therapies with antibi- otics, antiandrogenic hormones (estrogens), and retinoids [3]. ese therapies are associated with significant side ef- fects and thus could not be justified as a matter of course. e immune system is chiefly responsible for coordi- nating and regulating the disease progression and even remission. New theories regarding acne development pro- vide specific and rational directions for acne therapies. For Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2020, Article ID 3231413, 14 pages https://doi.org/10.1155/2020/3231413