Tongkat ali: Sukardiman et al., 2025

A 2025 systematic review in Heliyon identified 12 Indonesian plants traditionally used for erectile dysfunction and mapped their molecular targets using network pharmacology — finding convergence on nitric oxide signaling and androgen pathways. This is a mechanisms review, not a clinical trial: it shows what compounds might do in theory, not what happens when men actually take the plants.

Key takeaways

• The review identified 12 indigenous Indonesian plants used empirically for ED, including Eurycoma longifolia (tongkat ali), with molecular targets converging on NO/cGMP signaling and testosterone synthesis pathways.
• Network pharmacology maps compound-gene interactions — it's a hypothesis-generating tool, not a substitute for human trials.
• The authors found overlap between plant compound targets and known ED pathology genes, particularly in vascular and hormonal regulation.
• This is a mechanisms review: it tells us what might happen at the molecular level, not whether erectile function actually improves in men who take these plants.
• Of the 12 plants reviewed, tongkat ali has the most clinical trial support outside this paper — the others remain largely untested in controlled human studies.

The study

Sukardiman and colleagues published this systematic review and network pharmacology analysis in Heliyon in 2025 (PubMed). They searched PubMed, Scopus, and Springer for all years through the search date, screening articles via PRISMA guidelines. Twelve articles met inclusion criteria covering 12 Indonesian plants traditionally used for erectile dysfunction. The authors then used bioinformatics databases — GeneCards for compound targets, DisGeNET for disease targets — to map the molecular networks these plants theoretically modulate. They built protein-protein interaction networks using STRING and conducted Gene Ontology (GO) and KEGG pathway enrichment analyses. The goal: identify shared molecular mechanisms among these plants and see how they align with known ED pathology at the gene level. No human subjects were enrolled; this is a computational synthesis of existing data.

How to read this study

What this paper does well: The authors use established bioinformatics tools and databases to systematically map compound-gene-pathway relationships. The PRISMA flowchart ensures transparent article selection. Network pharmacology is valuable for hypothesis generation — it surfaces biological plausibility and helps prioritize which plants or compounds warrant clinical testing. The inclusion of both vascular and hormonal pathways reflects the multifactorial nature of erectile dysfunction.

What this paper is missing: This is in silico modeling — computational prediction, not experimental verification. Showing that a compound binds a target gene in a database does not prove it reaches that target at therapeutic concentrations in a living human. The review depends entirely on the quality of the 12 underlying articles, and the authors do not assess those articles' methodological rigor (sample sizes, controls, blinding). Most critically, network pharmacology cannot tell you dose, bioavailability, or clinical effect size. A compound might hit the "right" pathway and still do nothing measurable in a man's bedroom.

How I weight this paper: I treat this as a roadmap for what to test, not as evidence that these plants work. It's useful context — when I see tongkat ali show up in multiple clinical trials and its compounds map to androgen synthesis pathways here, that mechanistic coherence is reassuring. But I would never recommend a plant to a customer based solely on network pharmacology. The proof comes from randomized controlled trials measuring actual erectile function, testosterone levels, and quality of life — not from gene ontology enrichment scores.

What they found

The 12 plants identified were Eurycoma longifolia (tongkat ali), Tribulus terrestris, Zingiber officinale (ginger), Piper retrofractum, Kaempferia parviflora (black ginger), and seven others. Compound-target mapping revealed convergence on key pathways: nitric oxide/cGMP signaling (the same pathway Viagra targets), androgen receptor activation, antioxidant response, and anti-inflammatory cascades. GO analysis showed enrichment in biological processes like "response to hormone," "regulation of smooth muscle cell proliferation," and "nitric oxide biosynthetic process." KEGG pathway analysis highlighted the PI3K-Akt signaling pathway, MAPK signaling, and steroid hormone biosynthesis. Protein-protein interaction networks identified hub genes including AKT1, ESR1 (estrogen receptor alpha), AR (androgen receptor), and NOS3 (endothelial nitric oxide synthase). The authors concluded that these plants share molecular mechanisms consistent with improving both vascular and hormonal components of erectile function. No clinical outcomes — erection quality, IIEF scores, patient satisfaction — were measured or reported, because this was not a clinical study.

What it means for the average man

If you're considering tongkat ali or one of the other plants on this list, this paper tells you why they might work in theory — they appear to modulate pathways that matter for erections and testosterone. That mechanistic plausibility is a positive signal, but it's not the same as proof. Tongkat ali, specifically, has multiple RCTs showing real-world testosterone increases and improved sexual function metrics; the mechanistic overlay here is consistent with those findings. For the other 11 plants, this paper is mostly a hypothesis: "These deserve clinical trials." If you're already using a well-studied extract like standardized tongkat ali, this review supports the biological rationale. If you're considering a plant with no clinical trials behind it, you're still flying on traditional use and molecular guesswork — potentially valid, but not validated.

The caveats

Network pharmacology is only as good as the databases it draws from, and those databases are built largely on in vitro and animal studies. Human pharmacokinetics — absorption, metabolism, tissue distribution, excretion — are not modeled here. The 12 underlying articles were not quality-assessed; the authors accepted all included studies without weighting for rigor. The review also does not address dosing: hitting a pathway at 10 mg/day versus 400 mg/day can mean the difference between noise and signal. Industry funding and conflicts of interest in the source articles were not reported. Finally, this is a single review team's analysis; independent replication of the network findings would strengthen confidence. The editorial presents this as a starting point for drug development, not as a clinical recommendation — and that framing is appropriate.

Frequently asked questions

Sources

• Sukardiman, Mutiah R., Handayani R. (2025). Potential and mechanisms of indigenous Indonesian medicinal plants in treating sexual dysfunction: A systematic review and pharmacological network overview. Heliyon. PubMed
• Talbott SM, et al. (2013). Effect of Tongkat Ali on stress hormones and psychological mood state in moderately stressed subjects. J Int Soc Sports Nutr. (Example of clinical trial data on tongkat ali.)

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