Table 2.
Main characteristics of the included studies in this systematic review.
| Author, year | Study design, duration | Participants | Intervention | Control | Outcomes | Adverse effects | |
|---|---|---|---|---|---|---|---|
| N (intervention group/control group) | Acne classification (severity degree; classification system) | Herbal medicine; pharmaceutical form(s); dose/frequency; route(s) of administration | |||||
| Plant extracts | |||||||
| Bassett et al., 1990 [37] | RCT, 3 months | 61/63 | Mild to moderate; leeds system | Tea tree oil 5%; gel; cutaneous | Benzoyl peroxide 5% | Number of inflammatory and noninflammatory lesions | Intervention group: 44% of the participants reported dryness, itching, burning, and redness of the skin. Control group: 79% of the participants reported the same adverse effects. |
| Capitanio et al., 2012 [38] | RCT, 8 weeks | 30/30 | Mild; leeds system | A complex of zinc and an oligosaccharide derived from the seaweed Laminaria digitata; cream; twice a day; cutaneous | Placebo | Number of inflammatory and noninflammatory lesions; sebum production | Absence of irritation and skin peeling. |
| Enshaieh et al., 2007 [39] | RCT, 45 days | 30/30 | Mild to moderate; injury count | Tea tree oil 5%; gel; twice a day; cutaneous | Placebo | Number of total lesions; number of inflammatory and noninflammatory lesions; acne severity (ASI) | Intervention group: itching (N = 3); burning (N = 1); desquamation (N = 1). Control group: itching (N = 2); burning (N = 2). |
| Forest and Rafikhah, 2014 [40] | RCT, 30 days | 18/16 | Mild to moderate; leeds system | Camellia sinensis (aqueous extract of green tea); capsule; 500 mg/3 times per day; oral | Placebo | Number of total lesions; number of inflammatory and noninflammatory lesions | Without adverse effects |
| Fouladi, 2012 [41] | RCT, 4 weeks | 25/25 | Moderate to severe; injury count | Berberis vulgaris (aqueous extract of dried fruit); capsule; 200 mg/3 times per day; oral | Placebo | Number of total lesions; number of inflammatory and noninflammatory lesions; acne severity (Michaelson's acne severity score) | Without adverse effects |
| Hajheydari et al., 2014 [42] | RCT, 8 weeks | 30/30 | Mild to moderate; GAGS | Aloe vera topical gel combined with tretinoin cream 0.025%; gel; twice a day; cutaneous | Placebo + tretinoin | Number of total lesions; number of inflammatory and noninflammatory lesions; acne severity (ASI) | The intervention group reported fewer adverse effects than the control group |
| Hou et al., 2018 [43] | Uncontrolled trial, 4 weeks | 20 | Mild to moderate; NR | Panax ginseng (hydrophobic fraction in red ginseng ethanol extract); cream; 2 twice a day; cutaneous | — | Number of inflammatory and noninflammatory lesions; sebum production | NR |
| Khan and Akhtar, 2014 [44] | RCT, 12 weeks | (Female 1) 25/25 (Female 2) 25/25 |
Moderate; leeds system | (F1) Hippophae rhamnoides; (F2) Cassia fistula; emulsion; 500 mg twice a day; cutaneous; each powdered plant was extracted with 70% methanol solution |
Placebo | Sebum production; global clinical evaluation | NR |
| Kwon et al., 2014 [45] | RCT, 8 weeks | 34/34 | Mild to moderate; modified leeds system | Chamaecyparis obtusa fermented by Lactobacillus; cream; twice a day; cutaneous | Tea tree oil | Number of inflammatory and noninflammatory lesions; sebum production; acne severity (modified leeds system) | Intervention group: mild erythema (N = 2); skin dryness (N = 2). Control group: slight skin dryness (N = 4); moderate erythema and desquamation (N = 6). |
| Lee et al., 2011 [46] | RCT, 12 weeks | 50/47 | Mild to moderate; KAGS | Rosa combined with hexamidine disethionate 0.05% and retinol 0.03%; once a day; cutaneous | Adapalene 0.1% | Number of total lesions; number of inflammatory and noninflammatory lesions; acne severity (KAGS); global clinical evaluation; participants evaluation (TR) | The intervention group reported fewer adverse effects than the control group. However, by the end of the study, the difference between the two groups became negligible. |
| Lu and Hsu, 2016 [47] | RCT, 4 weeks | 40/40 | Moderate to severe; IGA | Camellia sinensis (decaffeinated green tea extract); capsule; 500 mg/3 times per day; oral | Placebo | Number of total lesions; number of inflammatory and noninflammatory lesions; life quality (CADI) | Intervention group: constipation (N = 1); abdominal discomfort (N = 2). Control group: polydipsia (n = 1); insomnia (N = 1). |
| Lueangarun et al., 2019 [48] | RCT, 12 weeks | 28/28 | Moderate to severe; GAGS | Garcinia mangostana (topical mangosteen extract in nanoparticle loaded gel, containing α-mangostin); gel; twice a day; cutaneous | Clindamycin 1% | Number of inflammatory and noninflammatory lesions; porphyrins production; clinical global evaluation; participants evaluation (TS) | Similar adverse effects in both groups. After 4-weeks of treatment, no participant had adverse effects on both sides of the face. |
| Malhi et al., 2017 [49] | Uncontrolled trial, 12 weeks | 18 | Moderate to severe; injury count and IGA | Tea tree oil; gel; twice a day; cutaneous | — | Number of total lesions; acne severity; participants evaluation (TR) | Well tolerated treatment. Moderate desquamation (N = 2); moderate skin dryness (N = 1). |
| Miglani and Manchanda, 2014 [50] | Uncontrolled trial, 6 months | 34 | NR; GAGS | Arctium lappa; 4 pills/4 times per day for 7 days followed by 7 days of placebo; oral | — | Number of total lesions; number of inflammatory and noninflammatory lesions; acne severity (GAGS); life quality (Acne-QoL) | NR |
| Orafidiya et al., 2002 [51] | RCT, 4 weeks | 112/ (1) 7 (2) 7 |
NR; injury count | Ocimum gratissimum essential oil; 0.25 cm3/twice a day; cutaneous | (1) Benzoyl peroxide 10% (2) Placebo |
Time necessary to reduce 50% of the total number of lesions (days) | Adverse effects are minimal and tolerable |
| Pan-In et al., 2015 [52] | RCT, 4 weeks | 10/10 | NR; injury count | Garcinia mangostana (cellulose-based nanoparticles as nano-reservoir and α-mangostin, an active component isolated from the edible Garcinia mangostana fruit); gel; twice a day; cutaneous | Placebo | Number of inflammatory lesions; acne severity (ASI) | NR |
| Pécastaings et al., 2018 [53] | Controlled trial, 56 days | 60 | Mild to moderate; GEA |
Myrtus communis leaf extract; cream; twice a day; cutaneous | Healthy volunteers, free of facial or dorsal acne and of any facial dermatosis | Acne severity; porphyrins production | Without adverse effects |
| Shafiq et al., 2014 [54] | RCT 45-days | 25/25 | NR; injury count | Casuarina equisetifolia bark extract 5% with 90% methanol; cream; twice a day; cutaneous | Benzoyl peroxide | Acne severity (Cook's Acne Grading Scale); global clinical evaluation | Intervention group: without adverse effects. Control group: 17% of participants reported skin irritation and redness. |
| Sharquie et al., 2006 [55] | RCT, 2 months | 30/30 | Mild to moderate; injury count |
Camellia sinensis; lotion; twice a day; cutaneous | Placebo | Number of inflammatory lesions; participants evaluation (TS) | Without adverse effects |
| da Silva et al., 2012 [56] | Controlled clinical trials, 21 days | 10/10 | Mild; NR | Copaifera langsdorffii essential oil; gel; twice a day; cutaneous | Placebo | Area occupied by the inflammatory lesions (mm2) | Without adverse effects |
| Sutono, 2013 [57] | RCT, 3 weeks | 45/41 | Mild to moderate; Lehman criteria | Garcinia mangostana (extract of mangosteen rind); capsule; 400 mg/3 times per day; oral | Placebo | Number of total lesions; number of inflammatory and noninflammatory lesions | Without adverse effects |
| Thappa and Dogra, 1994 [58] | RCT, 3 months | 10/10 | Severe (nodulocystic); injury count | Commiphora mukul (gugulipid, equivalent to 25 mg guggulsterone); 1 pill twice a day; oral | Tetracycline oral (500 mg) | Number of inflammatory and noninflammatory lesions | Without adverse effects |
|
| |||||||
| Combinations of plant extracts | |||||||
| Beltrami et al., 2001 [59] | Controlled clinical trials, 90 days | 15/15 | Mild to severe; NR | Krameria trianda, Serenoa repens, and Centella asiatica; cutaneous | Topical treatment + placebo (oral) | Sebum production | Intervention group: burning (resolved with continued treatment). |
| Lone et al., 2012 [60] | Uncontrolled trial, 45 days | 25 | NR; Cook's system of acne grading | Unani formulation: Irsa (Iris florentina), barghe neem (Azadirachta indica leaves), poste saras (Acacia speciosa bark), ghungchi safaid (Abrus precatorious), and Namake Sambhar (Lake salt) 50 grams each; 6 to 10 g/once a day; cutaneous | — | Acne severity (Cook's Acne Grading Scale) | Without adverse effects |
| Kim et al., 2019 [61] | RCT, 8 weeks | 28/28 | NR; injury count | Cheongsangbangpoong-tang formulation: Schizonepeta tenuifolia (0.5 g), Coptis japonica makino (0.5 g), Mentha arvensis var. iperascens (0.5 g), Ponciri Fructus Immaturus (0.5 g), Glycyrrhiza uralensis FISCH (0.5), Gardenia augusta (1.0 g), Cnidium officinale (1.0 g), Scutellaria baicalensis (1.0 g), Forsythia koreana (1.0 g), Angelica dahurica (1.0 g), Platycodon grandiflorum (1.0 g), Ledebouriella seseloides (1.0 g), corn starch (1.2 g), lactose hydrate (2.3 g); granulated; 5 g/3 times per day; oral | Placebo | Number of inflammatory and noninflammatory lesions acne severity (KAGS; IGA) | Intervention group: Digestion discomfort (n = 3). There were no serious adverse effects. |
| Lalla et al., 2001 [62] | RCT, 4 weeks | (G1) 23 (G2) 23 (G3) 5 (G4) 2 |
Mild to severe; Leeds system |
Ayurvedic formulation (soft extracts of Aloe barbadensis Miller, Azardirachta indica Juss, Curcuma longa Linn, Hemidesmus indicus Linn, Terminalia chebula Retzr, Terminalia arjuna Rob, and Withania somnifera Linn (one part of the extract approximately representing four parts of dried/fresh plant material); 2 pills/twice a day + topical preparation (gel (G1) or cream (G2))/twice a day oral and cutaneous | (G3) Placebo (topical preparation) (G4) placebo (oral and topical preparation) |
Participants evaluation (TR) | Mild itching (N = 2); increased gastric motility (N = 2). Reported adverse effects decreased with continued treatment. |
|
| |||||||
| Lubtikulthum et al., 2019 [63] | RCT, 12 weeks | 39/38 | Mild to moderate; modified leeds system | Allium cepa, Lavandula, Garcinia mangostana, Aloe vera, Morus papyrifera, and Melaleuca alternifolia; gel; 1 g/twice a day; cutaneous | Benzoyl peroxide 2.5% | Number of total lesions; number of inflammatory and noninflammatory lesions; life quality (DLQI); porphyrins production; participants evaluation (TS) | Most common adverse effect: Skin irritation. The intervention group reported fewer adverse effects (skin desquamation and erythema) than the control group. |
| Mazzarello et al., 2018 [64] | RCT, 30 days | (PTA) 20 (1) 20 (2) 20 |
Mild to moderate; injury count | Propolis 20%, tea tree oil 3%, and Aloe vera 10%; cream; twice a day; cutaneous | (1) Erythromycin 3% (2) Placebo |
Number of total lesions; number of inflammatory and noninflammatory lesions; acne severity (ASI); sebum production | NR |
| Orafidiya et al., 2004 [65] | RCT, 4 weeks | 48/ (1) 12 (2) 12 (3) 12 |
NR; injury count | Ocimum gratissimum essential oil 2%, and Aloe vera (25%, 50%, and 100%); lotion; 0.25 cm3/twice a day; cutaneous | (1) Placebo (2) Negative control (A. vera) (3) Positive control (clindamycin) |
Time necessary to reduce 50% the number of inflammatory lesions (days) | Intervention group: mild and tolerable adverse effects—96% of participants reported feeling a slight burning sensation on the skin. |
| Paranjpe and Kulkarni, 1995 [66] | RCT, 6 weeks | 67/15 | Moderate; injury count | 4 ayurvedic formulations; pills; 500 mg/3 times per day; oral | Placebo | Number of inflammatory and noninflammatory lesions; participants evaluation (TR) | NR |
| Parveen et al., 2009 [67] | RCT, 2 months | 20/10 | NR; IGA | Unani formulation; cream; twice a day; cutaneous | Placebo | Acne severity (IGA) | NR |
|
| |||||||
| Phytochemicals | |||||||
| Fabbrocini et al., 2011 [68] | Controlled clinical trials, 60 days | 20/20 | NR; GAGS | Resveratrol (0.01%, w/v); gel; once a day; cutaneous | Placebo | Acne severity (GAGS) | Without adverse effects |
| Jung et al., 2012 [69] | Uncontrolled trial, 8 weeks | 30 | Mild to moderate; injury count (inflammatory and noninflammatory lesions) | Polyphenon-60: catechin from green tea and is the representative green tea extract compound (20 mg/mL); lotion; twice a day; cutaneous | — | Number of inflammatory and noninflammatory lesions | NR |
| Yoon et al., 2013 [70] | RCT, 8 weeks | (Epigallocatechin-3-gallate 1%) 17/17 (Epigallocatechin-3-gallate 5%) 18/18 |
NR; modified Leeds system | Epigallocatechin-3-gallate 1% and 5%; solution; twice a day; cutaneous | Placebo | Number of inflammatory and noninflammatory lesions; acne severity (modified leeds system) | Intervention group (5%): erythema and skin irritation (N = 4). Intervention group (1%): without adverse effects. |
ASI: Acne Severity Index; CADI: Cardiff Acne Disability Index; DLQI: Dermatology Life Quality Index; GAGS: Global Acne Grading System; GEA: Global Acne Severity Scale; IGA: Investigator's Global Assessment; KAGS: Korean Acne Grading System; NR: not eported; TR: treatment response; TS: treatment satisfaction.