Senna Alata Extract
Senna Alata Extract
Senna Alata Extract
ABSTRACT
Objective. The study aimed to assess the efficacy and safety of Senna alata (akapulko) plant extracts compared
with topical antifungals in the treatment of superficial fungal skin infections.
Methods. A systematic review and meta-analysis of randomized controlled trials that studied patients with
diagnosed cutaneous tinea or dermatophytosis (excluding hair and nail), tinea versicolor, or cutaneous candidiasis, via
microscopy or culture, and compared the efficacy and safety of S. alata (akapulko) extract versus topical antifungals.
Two authors independently screened titles and abstracts of merged search results from electronic databases
(The Cochrane Skin Group Specialized Register, CENTRAL, MEDLINE, EMBASE (January 1990 to December
2011), Health Research and Development Information Network (HERDIN), and reference lists of articles), assessed
eligibility, assessed the risk of bias using the domains in the Cochrane Risk Bias tool and collected data using a
pretested Data extraction form (DEF). Meta-analyses were performed when feasible.
Results. We included seven RCTs in the review. There is low certainty of evidence that S. alata 50% lotion is as
efficacious as sodium thiosulfate 25% lotion (RR 0.91, 95% CI, 0.79 to 1.04; 4 RCTs, n=216; p=0.15; I2=52%) and
high quality evidence that S. alata cream is as efficacious as ketoconazole (RR 0.95, 95% CI, 0.82 to 1.09; 1 RCT,
n=40; p=0.44) and terbinafine cream (RR 0.93, 95% CI, 0.86 to 1.01; 1 RCT, n=150; p=0.09) in mycologic cure.
For adverse effects, there is very low certainty of evidence of increased harm with S. alata 50% lotion compared
to sodium thiosulfate 25% lotion (RR 1.26, 95% CI, 0.46, 3.44; 2 RCTs, n=120; p=0.65; I2=19%). Adverse effects
were few and mild.
Conclusion. S. Alata 50% lotion may be as efficacious as sodium thiosulfate 25% lotion and is as efficacious as
ketoconazole 2% and terbinafine 1% creams. There is insufficient evidence to compare the safety of S. alata 50%
lotion with sodium thiosulfate 25% lotion.
Key Words: Senna alata, Cassia alata, akapulko, skin fungal infections, dermatophytosis, tinea versicolor, pityriasis
versicolor, candidiasis, systematic review, meta-analysis.
Introduction
Adverse effects
Only two studies that compared S. alata 50% lotion
with STS 25% lotion as treatment for tinea versicolor noted
adverse effects.10,14 We were uncertain if S. alata lotion had
more adverse effects than STS lotion (RR 1.26, 95% CI
0.46, 3.44; 2n=120; p=0.65; I2=19%) (Figure 5).10,14 The most
common adverse effect for both treatments was pruritus. No
adverse effects were reported by participants in the study
which compared S. alata cream with ketoconazole cream as
treatment for dermatophytosis or tinea versicolor, and in the
study comparing S. alata cream with 1% terbinafine cream as
treatment for tinea versicolor.13,23
Figure 2. Risk of bias graph showing authors’ judgments about risk of bias Figure 3. Risk of bias summary showing
item across all included studies. authors’ judgments about each risk
of bias item for each included study.
Figure 4. S. alata 50% lotion versus STS 25% lotion, Outcome: Mycologic cure.
Figure 5. S. alata lotion versus STS 25% lotion, Outcome: Adverse effects.
Secondary Outcomes (because of high attrition rate) and imprecision due to small
sample size.
Clinical resolution (as reported by outcome assessors) There is high certainty of evidence that S. alata is as
One study (n=36) noted S. alata 50% lotion to be less efficacious as terbinafine for mycologic cure (RR 0.93, 95%
efficacious in clinical resolution of tinea versicolor than STS CI 0.86 to 1.01; 1 RCT, n=150) (Appendix 3: Summary
25% lotion (RR 0.63, 95% CI 0.40, 0.99; p=0.04).10 In one of Findings Table 2) There is high certainty of evidence
other study, it was uncertain whether S. alata cream was that S. alata is as efficacious as ketoconazole for mycologic
less efficacious than ketoconazole cream (RR 0.37, 95% CI cure (RR 0.95, 95% CI 0.82 to 1.09, 1 RCT, n=40) but low
0.02, 8.5; n=40; p=0.53) in achieving complete clearance of certainty of evidence that it is less efficacious for clinical cure
lesions of dermatophytosis and tinea versicolor.13 (RR 0.37, 95% CI 0.02 to 8.5; 1 RCT, n=40) (Appendix 3:
One study compared S. alata soap with two antifungal Summary of Findings Table 3.
soaps (Erythrophleum soap and Aframomum soap) in patients Lastly, there is very low certainty of evidence that S. alata
diagnosed with either tinea versicolor or tinea corporis. It soap is as efficacious as Erythrophleum soap (RR 1.15, 95%
was uncertain whether S. alata soap was more efficacious CI 0.65 to 2.06; 1 RCT, n=35), and more efficacious than
than Erythrophleum soap (RR 1.15, 95% CI 0.65, 2.06; n=35; Aframomum soap (RR 1.94, 95% CI 0.91 to 4.13; 1 RCT,
p=0.63), but there was a trend that it was more efficacious n=37) for mycologic cure. The evidence was downgraded
than Aframomum soap (RR 1.94, 95% CI 0.91, 4.13; n=37; twice due to significant risk of bias from lack of blinding of
p=0.09).24 participants and personnel, lack of pre-specified objectives or
outcomes, and a high number of dropouts.
DISCUSSION
Conclusions
This review included seven RCTs with 460 participants,
mostly patients with tinea versicolor, done in the Philippines This review suggests that S. alata lotion may be as
(5/7), medium-sized (median sample size=98), and efficacious as STS 25% lotion in the treatment of tinea
conducted in the 1990s to 2000s (6/7). The paucity of RCTs versicolor. Adverse effects were few and mild for both
using S. alata is quite striking considering that it is one of treatments and it is unclear whether there is a risk for
the ten medicinal plants recommended by the Department greater adverse effects due to S. alata lotion. Based on single
of Health in the Philippines. Four of the seven included studies, S. alata lotion may be as efficacious as terbinafine
trials used STS lotion as control. The World Health and ketoconazole creams.
Organization lists sodium thiosulfate as one of the topical
treatments for tinea versicolor.25 It acts as a keratolytic, Implications for research
enabling the removal of stratum corneum affected by There is a need for more adequately-sized RCTs with
dermatophytes, and as a fungistatic, particularly against good follow-up comparing S. alata with standard topical
Malassezia furfur, but its mechanism is unknown.26,27 Of antifungal drugs in the treatment of tinea versicolor,
note, current guidelines (NICE, UpToDate) and textbooks cutaneous dermatophyte infections, and candidiasis.
recommend topical antifungals such as azoles, allylamines,
selenium sulfide, and zinc pyrithione as treatment for Ethics review approval
superficial fungal infections.2,28,29 Although the goal of University of the Philippines-Philippine General
this review is to determine the efficacy of S. alata against Hospital (UP-PGH) Expanded Hospital Research Office
superficial fungal infections, majority of the studies focused (EHRO), October 2015 (2015-10-07-058)
on tinea versicolor, which is caused by yeasts. In addition, only
two, small-sized studies compared S. alata with established Study registration
antifungals: ketoconazole and terbinafine. UP Manila-Research Grants Administration Office,
There is low certainty of evidence that S. alata is as January 2018 (RGAO-2018-0014)
effective as STS 25% lotion for mycologic cure (RR 0.91,
95% CI 0.79 to 1.04; 4 RCTs, n=216) but less effective Statement of Authorship
for clinical cure (RR 0.63, 95% CI 0.40 to 0.99, 1 RCT, All authors participated in data collection and analysis,
n=36) (Appendix 3: Summary of Findings Table 1). The and approved the final version submitted.
evidence was downgraded due to a high risk for attrition
bias, as well as high heterogeneity between studies probably Author Disclosure
since one study had a longer treatment period. In terms of All authors declared no conflict of interest.
adverse effects, there is very low certainty of evidence that
S. alata has greater risk of harm than STS 25% lotion (RR Funding Source
1.26, 95% CI 0.46 to 3.44; 2 RCTs, n=120; I2=19%). The This paper was self-funded.
evidence was downgraded twice due to the high risk of bias
APPENDICES
Appendix 1. Characteristics of excluded studies
Study ID Reason for exclusion
Damodaran 199430 Not an RCT
Oladele 201031 Comparator was placebo