PRACTICAL VALUE OF RHINOCEROS HORN FROM AN EVIDENCE-BASED MEDICINE PERSPECTIVE AND THE POTENTIAL OF SUBSTITUTE MEDICINAL MATERIALS: A NARRATIVE REVIEW

PRACTICAL VALUE OF RHINOCEROS HORN FROM AN EVIDENCE-BASED MEDICINE PERSPECTIVE AND THE POTENTIAL OF SUBSTITUTE MEDICINAL MATERIALS: A NARRATIVE REVIEW

Nguyen Thi Kim Lien, Truong Mai Vinh Thoai
Faculty of Traditional Medicine, Hue University of Medicine and Pharmacy, Hue University

ABSTRACT

Objective: This article aims to synthesize and analyze scientific evidence regarding the therapeutic value of rhinoceros horn in Traditional Medicine, while also evaluating the pharmacological basis and applicability of substitute medicinal materials in order to suggest rational, sustainable, and biodiversity-conserving use of medicinal resources.

Methods: This study is a structured narrative review. Scientific literature related to rhinoceros horn and potential substitute medicinal materials was collected from international and regional databases, including PubMed, Google Scholar, CNKI, and Wanfang. The collected data were synthesized with a focus on biochemical studies, experimental pharmacology, clinical studies, systematic reviews, and network pharmacology analyses concerning rhinoceros horn and substitute medicinal materials.

Results: Current scientific evidence has not demonstrated any specific or superior therapeutic efficacy of rhinoceros horn. In contrast, several substitute medicinal materials have shown clear potential in terms of efficacy and practical applicability. Among them, Bubali Cornu (water buffalo horn) has been demonstrated to be a substitute with mechanistic similarity, exhibiting comparable antipyretic effects and clotting-time shortening effects at appropriately adjusted doses. In addition, medicinal herbs such as Moutan Cortex, Scutellariae Radix, Coptidis Rhizoma, and Rehmanniae Radix, as well as classical formulas modified by replacing or eliminating rhinoceros horn, including Qing Ying Tang and Xijiao Dihuang Tang, have continued to demonstrate efficacy in fever control, anti-inflammatory activity, and antibacterial effects.

Conclusion: Current evidence remains insufficient to establish a specific therapeutic role for rhinoceros horn. Alternative medicinal herbs have demonstrated potential applications in fever control, anti-inflammatory effects, and the supportive treatment of various related clinical conditions. Available data indicate that the use of alternative medicinal herbs represents a promising approach that is consistent with the development of Traditional Medicine in the modern context, contributes to biodiversity conservation, and warrants further evaluation through high-quality clinical studies.

1. INTRODUCTION

Throughout the history of medicine, particularly in East Asia, numerous animal-derived medicinal materials have been documented in traditional therapeutic practices. These medicinal substances not only possess medical significance but are also closely associated with cultural beliefs, folk experience, and healthcare practices passed down through generations [1]. However, in the context of modern medicine, which emphasizes evidence-based practice, the continued use of wildlife-derived medicinal materials requires careful reconsideration, especially as many species are facing severe population declines due to exaggerated claims regarding their medicinal effects, while illegal exploitation and trade continue to persist [2].

Rhinoceros horn (犀角 – Tê ngưu giác) represents a typical example of the intersection between traditional medical experience, social beliefs, and wildlife conservation issues. Recorded in classical medical texts for centuries, rhinoceros horn has been described as bitter and salty in taste, cold in nature, and associated with the Heart, Liver, and Stomach meridians. It is traditionally believed to possess the functions of clearing heat, cooling the blood, purging fire, and detoxification. Therefore, this medicinal material has commonly been used as a principal remedy for conditions such as high fever, eruptions, and hemorrhage caused by heat toxins [3].

The amplification of its purported benefits within communities, including unverified beliefs regarding its ability to cure various diseases, has contributed to sustained consumer demand and intensified global rhinoceros poaching pressure. The consequences of this demand extend beyond medical concerns, such as treatment safety and efficacy, and have become a serious challenge to biodiversity conservation. Currently, all five extant rhinoceros species are listed in the Red List of the International Union for Conservation of Nature with varying levels of threat. Rhinoceros horn has also been included in Appendix I of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), under which international commercial trade is prohibited in order to limit the risk of rhinoceros population extinction [4], [5].

Therefore, the therapeutic value of rhinoceros horn should be reassessed based on modern scientific evidence rather than relying solely on traditional records or folk beliefs. In the current context, a more appropriate approach is the objective evaluation of the pharmacological efficacy of rhinoceros horn while simultaneously identifying safe, legal, and scientifically supported substitute medicinal materials. Several substitute medicinal materials have been investigated with the aim of replacing the reported effects of rhinoceros horn while reducing dependence on wildlife-derived resources [6].

For these reasons, this narrative review was conducted to re-evaluate the role of rhinoceros horn from the perspective of evidence-based medicine, while also synthesizing currently available data regarding potential substitute medicinal materials. Through this approach, the study aims to contribute to the sustainable development of Traditional Medicine and directly support global biodiversity conservation efforts.

2. METHODS OF LITERATURE REVIEW

2.1. Literature Search Strategy

This article was conducted as a structured narrative review aiming to synthesize and analyze existing literature related to rhinoceros horn in Traditional Medicine, scientific evidence regarding its therapeutic efficacy, legal and conservation issues, as well as potential substitute medicinal materials. A narrative review approach was selected because the research topic encompasses diverse fields, including Traditional Medicine, evidence-based medicine, pharmacology, network pharmacology, wildlife conservation, and medicinal resource management policies.

Relevant literature was collected from scientific databases and information sources, including PubMed, Google Scholar, ScienceDirect, CNKI, Wanfang Data, specialized Traditional Medicine references, reports from international organizations such as the International Union for Conservation of Nature and the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), as well as legal documents and pharmacopeias related to the management, use, and substitution of rhinoceros horn.

The literature search was conducted through April 2026 using the aforementioned databases and information sources. No publication year restrictions were applied; relevant publications that met the study objectives and eligibility criteria were considered regardless of their publication date.

The search strategy was developed using combinations of Boolean operators (AND/OR) according to core vocabulary groups in English, Vietnamese, and Chinese, including:

– Terms related to medicinal materials: “rhinoceros horn”, “Cornu Rhinocerotis”, “sừng tê giác”, “Tê ngưu giác”, “犀角”, and “Xijiao”.

– Terms related to indications and therapeutic effects recorded in Traditional Medicine and modern research: “antipyretic”, “anti-inflammatory”, “fever”, “thanh nhiệt”, “lương huyết”, “giải độc”, “清热”, “解毒”, and “凉血”.

– Terms related to substitution and conservation aspects: “wildlife trade”, “water buffalo horn”, “Bubali Cornu”, “substitute”, “alternative”, “Thủy ngưu giác”, “thảo dược thay thế”, and “替代药”.

2.2. Inclusion and Exclusion Criteria

2.2.1. Inclusion Criteria

– Studies related to the biochemical nature, microstructural characteristics, and chemical composition of rhinoceros horn.

– Pharmacological and clinical studies, including preclinical studies (in vitro, in vivo) and clinical studies evaluating the therapeutic effects of rhinoceros horn, as well as studies assessing the potential of substitute medicinal materials.

– Review articles and literature reviews, with priority given to study designs providing high levels of evidence, particularly systematic reviews.

– Studies and reports addressing conservation aspects, including statistical data and official status reports from reputable international conservation and management organizations concerning rhinoceros exploitation, trade, and ecological risks.

2.2.2. Exclusion Criteria

– Literature with methodological limitations, including studies with weak designs, insufficient transparency in implementation, or substantial deviation from the original research objectives.

– Literature with limited accessibility, including duplicate reports across multiple databases or publications providing only abstracts without full-text availability.

– Non-scientific and non-academic evidence, including materials that did not undergo peer review, such as isolated subjective opinions, articles published in mass media, or non-academic publications.

2.3. Methods of Synthesis and Analysis

Following screening based on the predefined inclusion and exclusion criteria, a total of 25 publications were included in the review. Eligible studies were synthesized and analyzed using a qualitative approach. Full-text articles were reviewed, information was extracted, categorized by thematic content, and analyzed to clarify the scientific value of the available evidence. The data were grouped into four major categories: structural characteristics, biochemical composition, and bioavailability of rhinoceros horn; experimental and clinical evidence related to therapeutic effects; data regarding potential substitute medicinal materials; and information concerning consumption demand, trade, and conservation consequences.

The analytical process focused on comparing Traditional Medicine concepts with modern scientific evidence, while also evaluating study reliability, methodological limitations, and existing gaps in the literature. During literature management, content summarization, and information systematization, large language model (LLM)-based tools were used in a limited capacity as supportive instruments for preliminary data processing. The use of these tools did not replace the authors’ processes of full-text review, evidence quality appraisal, source verification, or academic interpretation.

3. RESULTS

3.1. Analysis of the biochemical nature and structure of rhino horn

Table 1. Biochemical nature and structure of rhino horn

Remarks: Scientific reports have not demonstrated any distinctive characteristics or specific value of rhinoceros horn. In addition, studies have concluded that rhinoceros horn is poorly degraded and absorbed in humans, while its compositional characteristics are highly similar to those of other animal horns, such as those of buffalo and cattle. These findings indicate that there is currently no scientific evidence demonstrating that rhinoceros horn possesses specific biochemical properties that distinguish it from other animal horn sources.

3.2. Re-evaluation of the clinical efficacy of rhino horn from the perspective of evidence-based medicine

Table 2. Summary of the efficacy evaluation of rhino horn regarding its antipyretic effect from the perspective of evidence-based medicine

Remarks: Results from studies indicate that the antipyretic effect of rhino horn is inconsistent. Clinical research on children shows that rhino horn is less effective at reducing fever than acetaminophen. While experimental studies on animals yield varying results depending on the experimental model, dosage, and route of administration, the majority show efficacy at doses higher than the equivalent doses in humans. Furthermore, its specificity has not been proven because substitute horns also have similar effects. Accordingly, the existing data do not provide a sufficient basis to support the use of rhino horn as an antipyretic therapy in clinical practice.

Table 3. Summary of efficacy evaluation of rhino horn regarding other pharmacological effects (anti-inflammatory, antibacterial, coagulation) from the perspective of evidence-based medicine

Remarks: Evidence indicates that rhino horn does not clearly demonstrate antibacterial effects or inflammatory inhibition at the cellular level. Although some experimental animal studies record analgesic, soft tissue anti-inflammatory, and clotting time-shortening effects, this efficacy is not superior to non-steroidal anti-inflammatory drugs (NSAIDs) or existing alternative medicinal materials. The anti-inflammatory efficacy of classical traditional formulas containing rhino horn is highly likely related to the synergistic effects of the other herbal ingredients. Studies also show the potential for substituting rhino horn with Water Buffalo Horn (Cornu Bubali) and Yak horn, possessing equivalent activities and effects.

3.3. Overview of potential medicinal materials as substitutes for rhino horn

3.3.1. Potential medicinal materials as substitutes for rhino horn

Table 4. Potential alternative medicinal materials for rhino horn

Remarks: Studies show that several alternative medicinal herbs possess a pharmacological basis consistent with the functional group of clearing heat, cooling the blood, detoxifying, and acting as anti-inflammatories in traditional medicine. Water buffalo horn demonstrates antipyretic effects and supports the blood coagulation process similarly to rhino horn. Publications also support the role of Water buffalo horn as a substitute medicinal material with a more appropriate biochemical, pharmacological, and legal basis. In certain herbs, active compound groups such as flavonoids, alkaloids, glycosides, saponins, etc., are recorded to have the ability to regulate biological targets related to the inflammatory response, including NF-κB, COX-2, iNOS, prostaglandins, and pro-inflammatory cytokines. Several medicinal materials also exhibit antibacterial or anti-inflammatory activities in experimental models.

3.3.2. Potential traditional formulas as substitutes for rhino horn

Table 5. Potential alternative traditional formulas for rhino horn

Remarks: Classical traditional formulas containing or previously containing rhino horn still maintain their biological activity when substituted with water buffalo horn or when rhino horn is completely removed in some experimental models. The efficacy of antipyresis, anti-inflammation, NF-κB inhibition, antibacterial activity, and support in improving bleeding conditions primarily reflects the synergistic effect of the multi-herb combination, rather than the specific role of rhino horn alone. These results support the feasibility of the strategy to replace rhino horn with appropriate and legally permitted medicinal materials. 

4. DISCUSSION

Rhino horn (Cornu Rhinoceri) is perceived as a highly valuable medicinal material, commonly used to clear heat, cool the blood, and detoxify. However, in the context of modern medicine emphasizing evidence-based practice combined with urgent challenges in global biodiversity conservation, the therapeutic value of this medicinal material needs to be objectively re-evaluated, while simultaneously clarifying the similarity of alternative medicinal materials to develop traditional medicine safely and sustainably.

4.1. Biochemical nature and structure of rhino horn

Inherently, rhino horn is a dense fibrous composite mass, a structure of epidermal origin, composed primarily of keratinized cells rich in α-keratin, cross-linked by highly stable disulfide bonds, and reinforced by components such as calcium salts and melanin [7], [8], [9]. This characteristic provides the horn with high mechanical durability but simultaneously reduces its solubility and degradability in the gastrointestinal tract. Pharmacokinetic evaluations indicate that the keratin network in rhino horn is practically undegraded by human digestive enzymes such as pepsin in the stomach or trypsin in the small intestine, thereby raising significant doubts about its bioavailability when ground into powder and administered orally. The absorption of valuable peptides or active ingredients (if any) through the intestinal mucosa into the systemic circulation is negligible, weakening the pharmacological basis of this treatment method [17], [18], [19]. 

Spectroscopic and high-performance liquid chromatography (HPLC) analyses of rhino horn reveal that the profile of 18 soluble amino acids and the content of essential trace inorganic elements (such as Fe, Zn, Ca, Mg) show no significant difference compared to water buffalo horn or yak horn, and can be completely substituted by daily common food sources [14], [15]. Thereby, elevating the medicinal value of rhino horn is an unfounded interpretation lacking scientific evidence. 

Research reports on its macroscopic and microscopic structures, as well as specific composition, have concluded that rhino horn does not possess unique characteristics or special structural components as claimed by word-of-mouth and unofficial sources. Furthermore, the notion of using this medicinal material to nourish and enhance health is also not supported by scientific evidence. 

4.2. Re-evaluation of the clinical efficacy of rhino horn from the perspective of evidence-based medicine

Although recorded in classical medical literature and used with functions such as clearing heat, cooling the blood, and detoxifying, modern scientific evidence has not yet demonstrated the specific therapeutic efficacy of this medicinal material. The majority of existing data comes from in vitro or in vivo studies, while the number of rigorously designed clinical trials remains very limited [30]. 

In a rare double-blind randomized clinical trial (RCT) evaluating the antipyretic effect in humans, the efficacy was noted to be unsustainable and fell short of expectations, only providing a mild and short-term reduction in body temperature (0.5ºC after 15 minutes, with no further increase in efficacy at subsequent time points) [19]. Experimental animal studies on the antipyretic effect also yielded inconsistent results, depending on the study model, dosage, and route of administration. Some studies recorded efficacy at high doses, but doses equivalent to human use typically showed no effect [6], [20], [21]. Notably, the antipyretic effect, if any, is not specific to rhino horn; substitute horns such as water buffalo horn or cattle horn also recorded similar efficacy [6], [18]. Regarding the purported effects of “detoxification” and anti-inflammation, existing evidence shows that rhino horn alone does not exhibit the ability to inhibit NF-κB in inflammatory cell models and lacks antibacterial activity against Bacillus subtilis or Pseudomonas syringae [22]. Several animal studies noted analgesic, soft tissue anti-inflammatory, or clotting time-shortening effects, but these effects were not superior to non-steroidal anti-inflammatory drugs or alternative medicinal materials [18], [21], [23]. These findings indicate that the functions described in the ancient literature still require further validation through high-quality modern studies.

Besides its unproven efficacy, the use of rhino horn also raises medical safety and ethical issues. Due to habitat characteristics, the surface of rhino horn can be contaminated and accumulate heavy metals [31]. Therefore, removing rhino horn from the Pharmacopoeia and enforcing a domestic and international trade ban across countries [30] is an appropriate adjustment in line with modern scientific data, ensuring patient safety and sustainability in traditional medical practice.

4.3. Potential substitute medicinal materials

4.3.1. Potential medicinal materials as substitutes for rhino horn

Current data suggest that many alternative medicinal materials have a clearer pharmacological basis than rhino horn, particularly on biological targets related to inflammatory responses, fever, and immune disorders such as NF-κB, COX-2, iNOS, prostaglandins, and pro-inflammatory cytokines. 

In terms of traditional medicine theory, Mu dan pi (Moutan Cortex – root of Paeonia suffruticosa) has the effect of clearing heat, cooling the blood, invigorating blood, and dispelling stasis, which is compatible with the classical functional profile of rhino horn. In terms of modern pharmacology, Moutan Cortex extract is noted for its strong ability to inhibit the activity of the NF-κB transcription factor by approximately 56-66%, whereas rhino horn alone does not exhibit a clear inhibitory effect; furthermore, it reduces the expression of inflammatory mediators such as COX-2, iNOS, and IL-8. Scutellaria baicalensis (root, Huang qin) and Coptis chinensis (rhizome, Huang lian) are also two herbs with high substitution potential within the heat-clearing and detoxifying group. Scutellaria baicalensis is rich in flavonoids such as baicalein, wogonin, and chrysin, capable of regulating arachidonic acid metabolism, prostaglandin synthesis, and inhibiting NF-κB activity. Meanwhile, Coptis chinensis contains alkaloids with antibacterial, anti-inflammatory, and COX-2 inhibitory activities. If rhino horn is primarily justified by the concept of “clearing heat,” then Scutellaria baicalensis and Coptis chinensis provide a more specific pharmacological foundation for the “detoxifying” effect, including the inhibition of inflammatory responses and the reduction of pyrogenic mediators. Rehmannia glutinosa (Sheng di huang) has the effect of nourishing yin, cooling the blood, and descending fire, making it suitable for syndromes of heat entering the blood level or high fever depleting bodily fluids. Although its NF-κB inhibitory effect is not as strong as that of Moutan Cortex or Scutellaria baicalensis, this medicinal material holds value in combinatorial formulations due to its immunomodulatory capacity and support in restoring homeostasis. Trichosanthes kirilowii root (Tian hua fen) stands out with its ability to inhibit intracellular inflammatory responses and act on the cell cycle. This makes Trichosanthes kirilowii root more suitable in situations exhibiting inflammation, swelling, or heat-toxin [27], [28].

Besides herbal medicines, Water Buffalo Horn is also proven to be a suitable substitute. Through the lens of metabolomics, Water Buffalo Horn demonstrates the ability to intervene in biological targets that regulate inflammatory and febrile responses. Experimental studies show that extracts from this material directly act on the arachidonic acid metabolic network , reducing the concentration of Prostaglandin E2 in the hypothalamus—the core neurotransmitter responsible for hyperthermia. Concurrently, this process decreases the release of pro-inflammatory cytokines such as TNF-α and IL-6, while protecting cerebral vascular endothelial cells by enhancing the activity of endogenous protective enzymes such as Superoxide Dismutase (SOD) and Catalase (CAT) [18], [25], [26]. 

Most of the current evidence is still derived from preclinical experimental studies, and the proposed alternatives are based on similarities in therapeutic targets and pharmacological mechanisms rather than on direct comparative trials with rhinoceros horn. Therefore, further well-designed clinical studies are needed to determine the indications, dosage, and safety of these alternative medicinal herbs. Nevertheless, the findings reported to date remain important for establishing a scientific basis and supporting the safer, more rational, and more effective use of alternative medicinal herbs.

4.3.2. Potential traditional formulas as substitutes for rhino horn

In traditional medical practice, rhino horn appears more frequently in classical formulas than as a standalone ingredient. Therefore, evaluating the substitutability of rhino horn at the formula level aligns with the combinatorial principles of traditional medicine, where therapeutic efficacy is often generated from the synergy among multiple groups of medicinal ingredients. 

Results obtained from in vivo animal experiments indicate that regarding the antipyretic effect, when rhino horn is entirely replaced by water buffalo horn in classical formulas such as Qing Ying Tang or Qingwen Baidu Yin, the stable and sustained body temperature-lowering effect is still maintained. The molecular biological basis for this effect is determined to be the synergistic interaction among the herbs, which inhibits the Cytochrome P450 enzyme system in the liver, thereby preventing the metabolism of arachidonic acid into the pyrogenic neurotransmitter Prostaglandin E2 (PGE2) in the hypothalamus [29], [30]. Analytical data also demonstrates that the synergistic power of herbs combined with Water Buffalo Horn in Xijiao Dihuang Tang excellently maintains the ability to inhibit pro-inflammatory transcription factors. In particular, a meta-analysis (17 RCTs, n = 1,147) showed that this formula also helps improve platelets, control bleeding, and yields a significantly higher clinical response rate in ITP patients compared to the Western medicine group (RR = 1.27, p < 0.05) [27], [28]. The synergistic interaction of these botanical drugs plays a pivotal role in preventing the overactivation of macrophages, halting the autoantibody generation process that destroys platelets, and protecting the integrity of the vascular endothelium. Similar research on versions devoid of rhino horn, such as Shen Xi Dan and Qing Gong Tang, showed that they still retained antibacterial activity against Bacillus subtilis [28].

Studies show that many formulas previously containing rhino horn still maintain their biological activity when rhino horn is substituted with water buffalo horn or removed from the recipe, suggesting that the role of rhino horn in these formulas may not be absolutely specific. The use of water buffalo horn or the combination of readily available herbs with clearer pharmacological mechanisms is an appropriate approach, simultaneously preserving the therapeutic principles of traditional medicine, meeting the requirements of evidence-based medicine, and aligning with the goal of conserving endangered wildlife.

4.4. Limitations of the study

This study is a narrative review rather than a systematic review; therefore, a systematic approach to the search, selection, and appraisal of the literature was not applied. The study did not assess the risk of bias of individual studies and did not perform quantitative analysis (meta-analysis) of the collected findings. In addition, some of the evidence regarding alternative medicinal herbs and herbal formulations is primarily based on preclinical experimental studies, while clinical evidence remains limited. Furthermore, the possibility of publication bias cannot be excluded, which may affect the completeness and generalizability of the synthesized evidence. Therefore, the findings of this study should be interpreted with caution, particularly with regard to clinical efficacy and the potential for direct substitution of rhinoceros horn.

5. CONCLUSION

A synthesis of the available evidence from evidence-based medicine, pharmacological studies, and review analyses indicates that there is currently no high-quality scientific evidence demonstrating that rhinoceros horn has specific or superior therapeutic efficacy compared with existing alternatives. The effects described in ancient medical literature, such as “clearing heat, detoxifying, and reducing inflammation,” have not been consistently demonstrated by modern scientific evidence, while the observed efficacy remains limited and inconsistent. In contrast, biochemical studies and preclinical experimental studies have demonstrated the potential of medicinal alternatives, such as Moutan Cortex, Coptis chinensis, Scutellaria baicalensis, Water Buffalo Horn, among others. Available data also indicate that many traditional herbal formulations retain certain biological activities and therapeutic effects after rhinoceros horn is replaced or removed. Therefore, there is currently no evidence that the complete removal of rhinoceros horn from clinical practice and pharmacopoeias would result in the loss of an irreplaceable therapeutic option in Traditional Medicine. The shift toward alternative treatment regimens using medicinal herbs or water buffalo horn not only facilitates the standardization of safer, transparent, and evidence-based treatment protocols but also reflects the strong ethical responsibility of the medical community in efforts to conserve global biodiversity.

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