Fereshteh Safavi
Adolfo Andrade-Cetto
Sonia M. Escandón-Rivera- Laboratorio de Etnofarmacología, Departamento de Biología Celular, Facultad de Ciencias, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
Traditional Persian Medicine (TPM) has long contributed to the diagnosis, prevention, and treatment of diabetes. Rooted in the theory of temperament, TPM classifies individuals and diseases according to four qualities: warm-dry, warm-wet, cold-wet, and cold-dry. In classical TPM literature, diabetes is referred to by various names—most notably “dhiabitos” and “dulāb”—and is consistently associated with dysfunction of the kidneys and liver. For this study, seminal TPM texts were systematically reviewed using targeted keywords to extract definitions, etiologies, symptoms, diagnostic criteria, and therapeutic strategies related to diabetes. These findings were supplemented with data from electronic databases, including ScienceDirect, PubMed, and Scopus. TPM classifies diabetes into two categories: hot and cold. Historical manuscripts detail a wide array of therapeutic preparations, predominantly herbal and herbo-mineral formulations, along with several mineral substances believed to balance temperament. Among these, oral dosage forms, particularly Safoofs (dry powders), were the most frequently prescribed across both categories. In total, 208 plant species from 81 botanical families, along with several mineral substances, were identified in traditional formulations. According to TPM, the medicinal plants, similarly to diseases, commonly exhibit either hot or cold properties, reflecting the principle that treatments should rebalance underlying dystemperament rather than merely relieve symptoms. This paradigm emphasizes addressing the root causes of disease. TPM physicians (hakims) often attribute diabetes to factors such as kidney dysfunction and dysregulated water metabolism. In contrast, modern biomedical literature does not distinguish between “hot” and “cold” diabetes; these classifications may reflect two stages in the spectrum of diabetes pathology. Hot diabetes may align with the early stages of Type 2 diabetes, while cold diabetes corresponds to the advanced stages of Type 2 diabetes or possibly Type 1 diabetes. Future research should examine the phytochemical and pharmacological profiles of plants used in the treatment of “hot” and “cold” diabetes, with a particular emphasis on their hypoglycemic properties. Plants used for “hot” diabetes may possess anti-inflammatory effects that protect pancreatic beta cells and improve insulin function. Additionally, it is important to explore the potential effectiveness of plants associated with “cold” diabetes in managing diabetes-related complications, such as nephropathy.
1 Introduction
1.1 Definition and overview of diabetes: a modern perspective
Globally, approximately 589 million adults aged 20–79 are living with diabetes mellitus. Elevated blood glucose levels occur when the body does not produce enough insulin, cannot effectively utilize the insulin produced, or both. Type 1 diabetes is typically an autoimmune condition characterized by the destruction of insulin-producing β-cells in the pancreas, resulting in an absolute deficiency of insulin. Although the exact causes remain unclear, both genetic predisposition and environmental factors play major roles. Thanks to modern treatments, individuals with type 1 diabetes can lead healthier lives and significantly reduce their risk of complications (ADA, 2025; IDF, 2025). Type 2 diabetes accounts for approximately 90% of all diabetes cases worldwide and is projected to become the second leading cause of disease burden by 2050. It is characterized by insulin resistance, a condition in which the body’s cells fail to respond effectively to insulin, prompting the pancreas to produce increasing amounts of insulin to maintain euglycemia. Over time, β-cell function may decline due to chronic overstimulation, leading to progressive insulin deficiency. Key risk factors include obesity, aging, ethnicity, and family history. Management primarily emphasizes lifestyle modifications, such as adopting a nutritious diet, engaging in regular physical activity, smoking cessation, and maintaining a healthy weight. When lifestyle interventions prove insufficient, oral agents such as metformin are commonly prescribed as first-line therapy. If target glucose levels remain unmet, dual therapy may be considered to enhance glycemic control, including sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, glucose-dependent insulinotropic polypeptide (GIP), and sodium-glucose co-transporter 2 (SGLT2) inhibitors (IDF, 2025).
Herbal medicine has been a significant and widespread facet of complementary and alternative medicine for thousands of years. Diabetics often turn to these medicines, either as a complementary therapy or as the main approach to improving their condition (Cruz and Andrade-Cetto, 2015; Itrat and Akhlaq, 2022). In this context, the rich reservoir of traditional medical manuscripts and local healers’ practices offer invaluable insights (Shankar and Liao, 2004). TPM, also known as “Sinai medicine,” represents a holistic medicine tradition whose history spans several centuries (Dabaghian et al., 2012). The World Health Organization acknowledges the significance of traditional medicines and supports their incorporation into national healthcare systems (WHO, 2023). Iran holds the third position in traditional medicine trials on the International Clinical Trials Registry Platform (ICTRP), highlighting its pioneering status in this field, following China and India (Juneja et al., 2020). In the annals of medical history, diabetes mellitus unfolds a fascinating story dating back 3,500 years. Diabetes diagnosis and treatment were extensively studied in Persian literature and clinical settings during the Middle Ages (Larijani et al., 2016). Sections 1.2 and 1.3 provide a concise overview of “TPM” and “Temperament,” underscoring their relevance in framing the present study. This review offers a comprehensive examination of diabetes through the lens of TPM, addressing its definition, cultural context, and the significance of temperament theory in disease interpretation. A central aim is to identify and describe, in detail, the historically utilized dosage forms and constituents of herbal preparations. Regardless of current evidence regarding efficacy, this study explores the properties, nature, and temperament of their ingredients. Herbal, mineral, and animal-derived components found in traditional formulations were systematically extracted, with rigorous efforts to match each historically named plant to its modern common or scientific nomenclature. By revisiting the historical application of TPM in diabetes management, we aim to encourage contemporary practitioners to draw insights from this ancient corpus of knowledge. Furthermore, we hope to foster deeper inquiry into conventional therapeutic approaches. To our knowledge, this is the first review to integrate these specific objectives, underscoring our unique contribution and opening new avenues for future research.
1.2 A brief historical background to TPM
As a holistic medical system, TPM has a long and fruitful history, originating in ancient Iran. Since ancient times, TPM has played a significant role in the diagnosis, prevention, and treatment of diseases in Persia (Rezaeizadeh et al., 2009). Rooted in practical experience and observations passed down through generations, TPM has evolved over time and has been enriched by medical knowledge from civilizations such as India, China, Egypt, and Greece (Gorji and Khaleghi Ghadiri, 2001). The TPM healers, known as “Hakims,” contributed to the development of the theory of the four humors, known as “Ákhlāt” in Persian, which later became a fundamental concept in global medicine (see section 1.3 for details) (Zargaran, 2014). Maintaining a balance between each humor has been crucial for body health. In TPM, the six basic principles (Sette-ye-Zarurieyeh) are considered the most significant factors in maintaining or losing health, which together form major aspects of a lifestyle. These factors include weather, food and drink, exercise, retention and excretion, sleep and wakefulness, and mental and emotional state (Aghili Alavi Khorasani Shirazi, 2006; Iranzadasl et al., 2021). According to this ancient doctrine, “medicine” refers to the knowledge of maintaining health and treating illness, with the former taking precedence (Arzani, 1915). In this respect, the TPM manuscripts, mostly written by Persian scholars in the Middle Ages, offer a treasure trove of knowledge about traditional medicine and pharmaceuticals, as well as an array of inventive studies, particularly about using medicinal plants in medicine (Schulz, 2023). For instance, the Qarabadin books are among the best-known pharmaceutical texts written by Persian scholars. These traditional pharmacopeias contain meticulously comprehensive lists of herbal medicine names, formulas and recipes describing how to prepare compound medicines. Qarabadin formulas differ from author to author.
1.3 Temperament theory in TPM: disease etiology
In TPM, fire, air, water, and earth are considered the four fundamental elements present in both human and non-human entities. Warmth, coldness, wetness, and dryness are the basic qualities associated with each of the elements. Fire is characterized by warmth and dryness, air by warmth and wetness, water by coldness and wetness, and earth by coldness and dryness. When these elements interact within composite bodies, a dominant configuration of qualities—referred to as “temperament” (Mezaj)—emerges, shaping the physiological and pathological nature of the organism (Avicenna, 2005). Temperament comprises four humors (khelts): “warm-dry (Sáfrā or yellow bile),” “warm-wet (Dám or blood),” “cold-wet (Bálghám or phlegm),” and “cold-dry (Sáudā or black bile)” (Naseri et al., 2009). Consequently, various substances—including medicines, herbs, and foods—possess distinct temperaments derived from the elemental qualities of heat, cold, wetness, and dryness (Avicenna, 2005). These temperaments influence physiological functions and pathological conditions in the human body. Within the framework of TPM, diseases are diagnosed based on an individual’s inherent temperament. An imbalance among these qualities is believed to precipitate disease, and treatment strategies aim to restore equilibrium through targeted dietary, herbal, and lifestyle interventions (Naseri et al., 2009).
1.4 Treatment approaches to diabetes in TPM
1.4.1 The importance of medicinal plants in diabetes treatment in TPM
Herbal medicine encompasses a range of products, including raw herbs, herbal materials, herbal preparations, and finished herbal formulations. The last two categories, herbal preparations and finished herbal formulations, include herbal drugs and their preparations that serve as the active pharmaceutical ingredients (APIs). These substances are derived directly from botanical sources. “Mixture herbal products” refer to formulations containing more than one herb and may also include excipients to support stability or delivery. In certain regulatory frameworks, herbal medicines may incorporate naturally occurring organic or inorganic substances of non-plant origin such as those derived from animals or minerals (WHO, 2007). In TPM, herbal remedies are employed to treat both types of diabetes using either single-herb formulations or mixture herbal products. Each herb is attributed to a distinct temperament based on its elemental qualities; therefore, prescribing the same herbal medicine for different types of diabetes without first evaluating the patient’s temperament is considered ineffective and potentially harmful. Mixture herbal products are formulated to maintain a deliberate balance among the constituent ingredients, considering their individual temperaments. To achieve this, TPM developed principles for determining the overall temperament of compound preparations—particularly those containing more than ten botanicals with varying profiles. The four fundamental qualities—heat, cold, wetness, and dryness—are graded on a scale from 1 to 4, reflecting increasing potency. Hakims calculated the final temperament of a formulation by weighing the dose and grading of each herb, ensuring therapeutic equilibrium within the preparation (Kabir, 2003).
1.4.2 Dosage form and mode of administration of herbal medicine
TPM manuscripts cover a wide range of therapeutic dosage forms and treatments. Diabetes dosage forms include several ones. These dosage forms are divided into two categories: oral and non-oral forms, each further subdivided.
2 Methodological approach
This review was conducted in three distinct phases. The first phase, historical text mining, involved a targeted search of authoritative sources among surviving Persian manuscripts dating from the 9th to the 18th centuries. Traditional knowledge was systematically extracted using Noor software (version 1.5), a searchable digital library comprising approximately one thousand TPM texts. Sources exhibiting low thematic relevance or superficial similarity were excluded using a modified PRISMA methodology (Figure 1). Following this process, 11 traditional texts were selected based on rigorous screening and final evaluation of thematic relevance. These books, endorsed by the Iran Food and Drug Administration, are supported by empirical evidence, possess historical validity, and are grounded in the philosophical principles that form the foundation of TPM. These books include Al-Hawi (1) (Razi, 2005), Al-Qanun fi al-tibb (2) (Avicenna, 2005), Al-Aghraz Al-Tabiyeh (3) (Jorjani, 2010), Tohfato Al'-Momenin (4) (Tonekaboni, 2007), Qarabadin-e-Kabir (5) (Aghili Alavi Khorasani Shirazi, 2007), Makhzan-Al’ Advieh (6) (Aghili Alavi Khorasani Shirazi, 2008), Makhazen al Taalim (7) (Khan, 2015), Kamil al-Sana’ah al-Tibbiyya (8) (Ahwazi, 2009), Exir-e-Azam (9) (Chashti and Nazem, 2008), Qarabadin-e-Aazam (10) (Chashti and Nazem, 2004), and Tebe-Akbari (11) (Arzani, 2009). The review focused on identifying content related to diabetes by using search terms such as “Dhiabitos,” “Dulāb,” and other relevant names listed in Section 3.1. Relevant material was systematically extracted, including definitions of diabetes according to conventional medical frameworks, clinical signs and symptoms, the two types of diabetes as classified in TPM, along with their distinguishing features and corresponding treatments, dosage forms previously prescribed for each type, and principles guiding the formulation of compound medicines, along with supplementary information. Additionally, all herbal and mineral constituents referenced in these dosage forms were documented. For each medicinal plant cited, data were recorded on traditional name(s), plant part(s) used, and temperament classification.
Figure 1. PRISMA flow diagram for included studies across three phases: historical text mining, botanical identification, and contemporary literature review.
In the second phase, botanical identification, significant effort was devoted to accurately assigning vernacular names to modern botanical taxa. Plant species cited in historical texts, mostly under Persian, Arabic, and Indian traditional names, were systematically compared with contemporary scientific classifications. To ensure the highest level of accuracy, the study relied on historical ethnobotanical identification literature, including several authoritative Persian treatises and ethnobotanical glossaries, to correlate ancient nomenclature with accepted botanical equivalents (Figure 1) (Tonekaboni, 2007; Aghili Alavi Khorasani Shirazi, 2008; Unani Pharmacopoeia of India, 2008; Ghahreman and Okhovvat, 2009).
The third phase, contemporary literature review, involved searches in modern scientific databases to supplement and contextualize findings. Regional flora databases [World Flora Online (www.worldfloraonline.org), International Plant Names Index (IPNI) (www.ipni.org), and the Medicinal Plant Names Services (MPNS)] were used to validate the individual identifications and to determine the family genera of each plant. In cases where the correspondence between the traditional name of a plant and its scientific name was uncertain and where several plants were referred to by that traditional name in contemporary texts, all relevant plants were mentioned. Scientific databases such as ScienceDirect, PubMed, and Scopus were also used for targeted searches for complex terms and to supplement conventional literature.
3 Results and discussion
3.1 Diabetes and herbal therapeutics in TPM
3.1.1 Types of diabetes: TPM insights
“Dhiabitos,” a Greek word that entered Persian manuscripts, and “Dulāb,” a Persian word, describe the same symptoms of diabetes in the TPM books. Polyuria, polydipsia, and thirst are main symptoms. Dulāb in Persian means “water wheel” in which water is constantly turning from one side to the other, so diabetes was conceptualized as dulāb because of the constant thirst and polyuria (Arzani, 2009). Diabetes was introduced in TPM texts under other names, including “Diyanitas,” “Diasquoms,” “Dhiaskous,” and “Qaramis,” which are Greek words, and “Aldawaarat,” “Alduwlab,” “Zalaq al-kuliyyah,” “Zalaq al-Am’aa al-kuliyyah,” “Zalaq al-mizaj,” and “almaebar,” which are Arabic (Baghdadi, 1983). Considering the definition, dhiabitos was found to be strongly correlated with kidney and liver function. Apparently, the retention force of the kidneys (conceptualized as the kidney’s ability to concentrate urine) is reduced and may therefore be characterized by excessive urine output. The hot temperament of the kidneys led to an increase in the absorption of moisture and water from the liver and stomach into the kidneys. This phenomenon was found to be another etiologic symptom (Rezaeizadeh et al., 2009; Jorjani, 2010; Khan, 2015). In TPM, diabetes is divided into two categories: “hot diabetes” (Dhiabitos-e-har) and “cold diabetes” (Dhiabitos-e-bared), both with specific symptoms. From this perspective, diabetes patients have either hot or cold dystemperaments (Sou-e-mezaj), so diagnosis and treatment are based on clinical symptoms. Table 1 lists the symptoms of these two diabetes types. In the past, hot diabetes had the highest number of diabetics. In TPM, herbs that cleanse and hydrate the liver and reduce excessive heat play a crucial role in the treatment of hot diabetes. These herbs are believed to help remove excess bile from the blood, balance the liver’s temperament, enhance the kidneys’ ability to eliminate excess heat and toxins from the body, and reduce symptoms associated with hot diabetes (Chashti and Nazem, 2004; 2008). The TPM text states that cold diabetes is caused by Sáudā dominance in the body and is more common in women and obese people. It is said that it occurs under stress (Avicenna, 2005; Chashti and Nazem, 2008; Jorjani, 2010). As part of TPM treatment, strengthening the heart, brain, and liver and eliminating Sáudā side effects are among the measures used to treat cold diabetes.
Table 1. TPM classification of diabetes.
3.1.2 Bridging traditional and modern diabetes perspectives through symptomatology
The classification of diseases varies across cultures, reflecting differing conceptual perceptions of illness. In traditional medicine, diagnosis is generally symptom-based, whereas modern medicine relies on an integrative approach that includes clinical symptoms, laboratory analyses, imaging techniques, and functional assessments. In this context, our understanding of diabetes and its treatment has evolved remarkably over the last century. From the identification of the pancreas’s role in the 19th century to the recognition of insulin resistance as a key factor in type 2 diabetes during the 1980s, our conceptual framework has undergone a profound transformation (March et al., 2022). According to the most important manuscripts in TPM, the disease dhiabitos and what is now known as diabetes mellitus share some similarities. Weight loss, unusual thirst, and polyuria were some of the main similarities. However, modern literature generally does not differentiate between hot and cold diabetes, so the term “hot and cold diabetes” may not actually refer to two distinct types of diabetes, such as Type 1 diabetes or Type 2 diabetes, but rather to two stages on the spectrum of diabetes pathology. The symptomatology described in Table 1 shows that at least three main symptoms, such as frequent urination, intense thirst, and weight loss, can reflect the early stages of Type 2 diabetes, suggesting that hakims’ concept of hot diabetes may be relevant in this regard. A fast heart rate (tachycardia) is not exclusively associated with diabetes but can be alarming when present with polyuria and other diabetes symptoms. These symptoms are common in people with diabetes mellitus with poorly controlled blood glucose levels. High blood glucose levels can lead to various complications, including cardiovascular and kidney problems. In an attempt to excrete excess glucose, it can lead to dehydration and trigger a rapid heart rate (Harkins, 2016). In contrast, the symptoms of cold diabetes such as moderate thirst, sexual dysfunction, neuropathy-related symptoms such as tingling, and gastrointestinal problems such as constipation, indigestion, and reflux can indicate either the advanced stage of Type 2 diabetes or possibly Type 1 diabetes (ADA, 2025; ElSayed et al., 2025). This distinction may provide insight into the increased libido observed in individuals with hot diabetes. Since hot diabetes is associated with an elevated metabolic state, early-stage patients may experience heightened energy levels, potentially leading to an increase in libido. Comparing libido between individuals with hot diabetes and those with cold diabetes, it is likely that the former exhibit higher levels of sexual desire. Therefore, it is conceivable that hakims observed and documented libido levels in relation to the distinct conditions of hot and cold diabetes rather than against a baseline of normal physiological function in healthy individuals. To refine our understanding of traditional diabetes concepts, it is essential to interpret the pharmacological and phytochemical properties of the plants used in the past to treat these diseases. It is likely that such an analysis will give us a better understanding of how these two types of diabetes in TPM fit into the modern and advanced definition of diabetes, provide deeper insights into the mechanisms of action and therapeutic effects of these drugs, and bridge the gap between traditional knowledge and modern science.
3.1.3 Relationship between the plants recommended in TPM for diabetes treatment and their therapeutic properties
This correlation highlights the multifaceted rationale underlying plant selection in TPM for diabetes management. Several therapeutic qualities recur among the medicinal plants traditionally recommended, each contributing to symptom relief or modulation of disease mechanisms. Astringent plants are commonly prescribed to counteract renal tubule dilation by promoting contraction, thereby aiding water retention. The laxative plants counter the average patient’s tendency toward dryness, which can lead to constipation. Therefore, these plants do not address the disease itself, but rather one of its symptoms. Strengthening plants help alleviate kidney weakness by enhancing renal tubule tone and preventing excess water loss, supporting the kidneys’ overall strength and functionality. Cold and cooling plants are indicated to mitigate excessive renal heat, which draws in water, while hot and warming plants target general bodily or hepatic/renal coldness, believed to impair kidney function. Moisturizing plants, in turn, alleviate persistent thirst, one of the hallmark symptoms in diabetic conditions (Paavilainen, 2009). Table 2 presents a summary of these traditional therapeutic categories along with representative plant species associated with each quality. These therapeutic properties are aimed at combating both the causes and symptoms of diabetes. They are designed to treat diabetes caused by an imbalance of cold and heat, although the treatment of cold-induced diabetes obviously takes precedence (Paavilainen, 2009). Different medieval healers held different views on diabetes treatment therapeutic qualities, resulting in various treatment formulas. A comparison of their theories reveals two universally recommended medicinal qualities: “cold” and “hot.” These qualities aim to counteract the main causes of diabetes, heat and cold, and emphasize the importance of addressing the causes of the disease and not just treating the symptoms. In the TPM, each medicinal plant mentioned has at least one of these qualities. Boswellia sacra Flück., for example, has three qualities, namely, astringent, hot and warming, and strengthening or Aloe vera (L.) Burm. f. (Warm-dry) has two qualities: astringent and laxative. Interestingly, the number of qualities associated with a plant has no significant impact on its popularity if it has at least one suitable quality. In this regard, diabetes therapy primarily targets what it perceives as external causes of kidney weakness and water retention, namely, heat and cold. In cold diabetes, where the weakening of the kidney and its ability to retain moisture are impaired, TPM recommends the use of plants with a hot or warming temperament to counteract this effect. In addition, rubefacient plants or alternatively astringent plants are recommended to constrict the kidney channels and support moisture retention. Strengthening plants are also recommended to address kidney weakness in these cases (Avicenna, 2005).
Table 2. Therapeutic qualities of plants recommended in TPM for diabetes treatment.
3.2 Dosage form and mode of administration of medicines at TPM
Persian scholars have named many natural pharmaceutical dosage forms from the remaining Persian books. They are determined not only by the pharmaceutical form, but also by the route of administration, ingredients, and therapeutic effect. Over 226 dosage forms are mentioned in the TPM literature. The final list of dosage forms was reduced to nearly 60 items, as many were related only to the preparation methods (Baranifard et al., 2017). Table 3 summarizes the most common oral and non-oral dosage forms used to treat hot and cold diabetes in TPM, based on data from the texts included in this paper. It contains the names and definitions of the herbal mixture products selected from the reviewed traditional texts. It seems that in that time, oral dosage forms, especially safoofs, dried oral powders, were the most prescribed dosage forms for diabetes and kidney disease. Table 4 lists the ingredients in each mixture herbal product, as well as the amount of each herb required for the formulation. Additionally, preparation methods are summarized. Despite their standard names, weights and measures were used differently during different historical periods, communities, and regions. Furthermore, pharmacological weights can be classified in three groups: specific, semi-specific, or non-specific. A specific weight can be converted to the metric system. Weights are defined as semi-specific if they refer to a cupful, a few handfuls, or the weight of a nut or lentil, or as non-specific when referring to terms such as “part” (juz’i), “quantity” (meqdār), and the like (Kahl, 2007). Non-specific weights enabled practitioners to adjust formulations according to the resources at hand or the situation, which is essential in traditional practices where precise measurements were often impractical. These terms illustrate a cultural perspective on measurement that contrasts with contemporary standards. All the prescriptions studied in Table 4 used specific weights, except in a few cases where semi-specific weights were used. Table 5 gives conversion factors for each traditional weight unit to its modern equivalent (Fakhouri and Khowam, 2018). These findings reveal the medieval history of TPM pharmacy.
Table 3. Common dosage forms for diabetes in TPM.
Table 4. Ingredients and preparation methods for mixture herbal products used in diabetes treatment in TPM.
Table 5. Conversion factor of each traditional weight unit to its modern equivalent.
3.3 Principles of formulating compound medicines in TPM
In TPM, all bodily functions are governed by the “ruling power,” which is regarded as the body’s primary healer and regulator. Its influence on the human organism is exerted through “the naturals,” a system of seven components. The first component is “the elements” (Arkan), with each of the four elements possessing distinct qualities, as previously described. The other components include the humors (Akhlat), temperaments (Mezaj), organs (A’za), spirits (Amah), faculties and forces (Qova), and functions (Afal). Together, these principles form the intellectual foundation of TPM theories, which serve as the basis for creating and formulating compound medicines. Like other Eastern medical traditions, TPM commonly employs compound medicines, particularly mixture herbal preparations. The formulation of such preparations is guided by two key determinants: the intrinsic characteristics of medicines and the complexity of the disease being treated. The intrinsic characteristics of medicines include six aspects. Firstly, regulatory effect: adjusting medicines’ potency by combining substances to achieve the desired effect. Secondly, corrective effects: counteracting dominant properties with adjuvants or supportive medicines. Thirdly, dispersing effects: improving the permeability of medicine and preventing dispersion by combining it with rapid penetration-enhancing organ-specific substances. Fourthly, detoxifying effect: neutralizing side effects or toxicity. Fifthly, pleasant effect: masking unpleasant odors or tastes with substances such as honey or saffron. Sixthly, protective effects on noble organs: reducing potency or strengthening sensitive organs with protective substances such as sugar or quince wine. In the case of disease complexity, there are three distinct aspects. Firstly, the disease consists of two humors: a single medicine cannot remove both humors alone. Secondly, the single medicine has two potencies: one weaker and one stronger in relation to the cause of the complex disease. It is necessary to combine it with a medicine that can attenuate both potencies. Chamomile, for example, has more resolve than its astringent property. So, if a strong astringent effect is required, it should be combined with an astringent. Thirdly, in complex diseases, one of the causes is stronger than the others. In this case, a combination of preparations that strengthen one of the potencies is required (Aghili Alavi Khorasani Shirazi, 2007; Paavilainen, 2009).
3.4 Mineral stones
In TPM, various minerals and stones are recognized for their therapeutic potential, particularly in the treatment of diabetes alongside botanical and animal-derived substances. Table 4 footnotes elaborate on several mineral sources, among which one notable example is the bezoar—a substance historically regarded as an antidote. This soft, layered stone resembles the structure of a pearl or an onion. While animal-derived bezoars are traditionally extracted from goats in India and from sheep and male goats in Iran, the reference here pertains specifically to a mineral-based bezoar. Known in Arabic as hajar al-sam, in Persian as Pādzahr kāni or FadZahar Madani, and in Indian traditional medicine as Zahar Mohra, this mineral antidote is attributed with medicinal properties and has been incorporated into TPM formulations. (Duffin, 2012). It is a mineral stone that occurs in different colors. It is found in regions such as China, Tibet, Kandahar, Kermanshah, Khorasan, Kerman, Turan, and Khulais, which are near Medina. The highest quality is “Khatayi.” Bezoar stones were highly regarded as alexipharmic agents in the 16th and 17th centuries (Duffin, 2013). In traditional medicine, bezoar is recognized for its properties that include clearing the heart, opening the body, cooling the liver, alleviating heat, and detoxifying both the liver and heart (Li et al., 2024). These effects appear to help restore balance when imbalanced humors arise during diabetes.
One of the most well-known healing clays is “Armenian bole,” which has been utilized for many purposes throughout history. In addition to its medicinal properties, this clay serves as a pigment, a base for oil painting, and in the gilding process (the application of gold leaf to intricately carved wooden items, often found on altarpieces and church altars). It is also employed in bookbinding (Gomes and Rautureau, 2021). Armenian bole is absorbent, astringent, detoxifying, antipyretic, and cooling (Hosseinkhani et al., 2025). In TPM, astringents are used to balance excessive moisture or fluidity in the body by promoting contractions and enhancing water retention in the renal system. Consequently, in cases of excess phlegmatic humor, the astringent properties of Armenian bole may help restore balance by reducing this excess.
Ambergris, a rare substance extracted from whale’s digestive tract, is traditionally valued for its invigorating effect. It is a dense, accumulating fecal mass sometimes found in both the Sperm Whale and the Pygmy Sperm Whale (Plön, 2022). This substance is classified as a cololite, which refers to a fecal mass that forms in the digestive tract. Ambergris can be divided into two subgroups: intestinalite (stored in the body cavity) and evisceralite (stored outside the carcass). Ambergris has been used for various purposes, including as medicine, a flavoring agent, an aphrodisiac, and a fixative in perfumes (Duffin, 2015). Ambergris has been used as a tonic for the brain, heart, and vital organs, and is also utilized in the treatment of neurological disorders (Kumar Singh et al., 2018). In traditional medicine, diabetes is considered a systemic disease that impacts multiple organs and systems. By strengthening the noble organs and addressing their weaknesses, ambergris may help the body manage the imbalances associated with diabetes more effectively.
Hajar ul Yahood is a fossilized stone traditionally recognized for its significant role in addressing urinary disorders, including urolithiasis. Mostly composed of calcium silicate, this mineral has been extensively used in Unani medicine to facilitate kidney stones’ dissolution, either as a powder or in combination with other therapeutic agents (Makbul et al., 2018). Considering that TPM emphasizes the role of the kidneys and their temperament in the context of diabetes, the use of Hajar ul Yahood may have been viewed as enhancing kidney function and supporting overall kidney health in individuals with diabetes.
Table 4 shows that noble metals such as silver and heavy metals such as tin, mercury, and arsenic are used as medicines. In TPM, arsenic compounds are called red and yellow zarnikh, including golden arsenic sulfide (As2S3, yellow in color) and Realgar (As4S4, red arsenic) (Carter et al., 2021). Historically, poisons and toxic substances were commonly used as medicines in various ancient medical traditions, including Traditional Chinese Medicine and TPM. These substances were regarded as potent remedies for serious ailments, believed to restore humoral balance and detoxify the body, thereby promoting overall health. Drawing from alchemical traditions, they were seen as transformative agents capable of purifying the body. Practitioners based their practices on empirical observations, acknowledging that certain toxic substances could produce beneficial effects. This demonstrates a complex understanding of health, where the distinction between poison and medicine was often unclear (Liu, 2021).
3.5 Medicinal plants in diabetes treatment
A total of 208 plant species from 81 botanical families have been identified as individual remedies or used in combination. Table 6 summarizes their traditional and common names, scientific classifications, botanical families, plant parts used, and temperaments as cited in TPM sources. The four most represented families are Fabaceae (14 species, 7%), Asteraceae and Apiaceae (13 species each, 6.5%), and Lamiaceae (12 species, 6%). The most utilized plant parts include seeds (31%), roots (22%), and fruits (17.5%). While all plants listed in Table 6 were recommended for managing both types of diabetes, either alone or in combination, Table 4 highlights certain preferred species that are more frequently cited in the dosages and formulations for both types of diabetes. These species include Astragalus gummifera Labill. (Moderate, slightly wet), Bambusa bambos (L.). Voss (Cold-dry), Berberis vulgaris L. (Warm-dry), B. sacra Flück. (Warm-dry), Camphora officinarum Boerh. ex Fabr. (Cold-dry), Cichorium intybus L. (Warm-dry), Coriandrum sativum L. (Cold-dry), Crocus sativus L. (Warm-dry), Cucumis sativus L. (Cold-wet), Cyperus longus L. (Warm-dry), Glycyrrhiza glabra L. (Warm-dry), Hordeum vulgare L. (Cold-dry), Lactuca sativa L. (Cold-dry), Oxalis acetosella L. (Cold-dry), Papaver somniferum L. (Whole plant: Cold-dry; Seeds: Cold-wet), Portulaca oleracea L. (Cold-dry), Punica granatum L. (Cold-dry), Quercus ilex L. (Warm-dry), Rhus coriaria L. (Cold-dry), Rosa × damascena Herrm. (Flower: Moderate, slightly Cold-dry; Rosewater: Moderate, slightly warm; Oil and Achnese: Warm-dry), Santalum album L. (Cold-dry), Vachellia nilotica subsp. tomentosa (Benth.) Kyal. & Boatwr. (Samq-e-arabi: Moderate, slightly dry; Aqāqia: Cold-dry), and Vitis vinifera L. (Warm-wet).
Table 6. Ethnopharmacological specifications of plant species used to treat diabetes in TPM.
3.6 Proposing a framework for future studies
Considering the historical use of mixture herbal products by Persian practitioners for diabetes treatment, future research may focus on the individual constituents of these medicinal remedies. As the next step, we propose a separate review to systematically evaluate the phytochemical and pharmacological profiles of plants associated with the treatment of “hot” and “cold” diabetes, with a specific focus on their hypoglycemic effects. Plants used to treat “hot” diabetes, such as Cucurbita pepo, Citrullus lanatus, and Melissa officinalis, act as cooling agents and may possess anti-inflammatory properties that could contribute to the protection of pancreatic beta cells and the enhancement of insulin function. Future research should investigate these properties, particularly their ability to improve insulin sensitivity and mitigate oxidative stress, especially through mechanisms related to AMPK activation. Conversely, we recommend exploring plants associated with “cold” diabetes, such as Zingiber officinale, Foeniculum vulgare, and Cinnamomum iners, for their potential effectiveness in managing diabetes-related complications like nephropathy. Specifically, studies could investigate the antifibrotic properties of plants such as Asparagus racemosus in diabetic nephropathy models. By investigating the pharmacological and phytochemical profiles of these traditional remedies, we can gain a deeper understanding of their therapeutic potential and evaluate their integration into diabetes therapies. Additionally, exploring the synergistic interactions among these herbs in the context of mixed herbal products is essential. This approach will enhance our understanding of their collective efficacy and contribute to the development of informed practices in diabetes treatment with traditional herbal medicine.
4 Conclusion
This review highlights the historical perspective of TPM regarding diabetes, particularly its classification into “hot” and “cold” types. While TPM provides valuable insights into past therapeutic approaches, it is important to acknowledge that the concept of temperament may not align with contemporary evidence-based principles. This study identifies various dosage forms and ingredients used in traditional remedies, emphasizing the need for a deeper understanding of their potential pharmacological effects. In this study, approximately 208 plant species from 81 botanical families were identified as most traditional medicine remedies, which were presented as single or mixture herbal products for diabetes treatment. Each of these plants possesses at least one of several essential qualities believed by medieval healers to play an important role in the treatment of the disease. In addition, by correlating historical names of medicinal plants with contemporary equivalents, this review not only preserves cultural heritage, but also opens new avenues for exploring the therapeutic potential of these plants in modern herbal medicine. The concept of “hot and cold diabetes” likely represents the different stages of diabetes progression in modern literature. “Hot diabetes” aligns with early stages of Type 2 diabetes with symptoms such as frequent urination, intense thirst, and weight loss. In contrast, “cold diabetes” corresponds to advanced stages of Type 2 diabetes or possibly Type 1 diabetes with symptoms such as moderate thirst, neuropathy, and digestive problems. Future research should focus on the phytochemical and pharmacological profiles of plants associated with the treatment of “hot” and “cold” diabetes, emphasizing their hypoglycemic properties. Plants utilized for “hot” diabetes may exhibit anti-inflammatory effects that help protect pancreatic beta cells and enhance insulin function. Furthermore, it is important to investigate plants associated with “cold” diabetes for their potential effectiveness in managing diabetes-related complications, such as nephropathy.
Author contributions
FS: Formal Analysis, Investigation, Methodology, Writing – original draft, Writing – review and editing. AA-C: Conceptualization, Funding acquisition, Supervision, Writing – original draft, Writing – review and editing. SE-R: Formal Analysis, Writing – review and editing.
Funding
The author(s) declare that financial support was received for the research and/or publication of this article. FS acknowledges This work was supported by Universidad Nacional Autónoma de México Postdoctoral Program (POSDOC). This project was partially sponsored by DGAPA, PAPIIT project IN214225.
Conflict of interest
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The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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Keywords: traditional Persian medicine, diabetes, temperament, hot diabetes, cold diabetes
Citation: Safavi F, Andrade-Cetto A and Escandón-Rivera SM (2025) Diabetes and traditional remedies in Medieval Persia: a historical perspective. Front. Pharmacol. 16:1673440. doi: 10.3389/fphar.2025.1673440
Received: 25 July 2025; Accepted: 27 October 2025;
Published: 12 November 2025.
Edited by:
Dâmaris Silveira, University of Brasilia, BrazilReviewed by:
Jaroslav Pejchal, University of Defence, CzechiaAshish Vishwakarma, Delhi Pharmaceutical Sciences and Research University, India
Copyright © 2025 Safavi, Andrade-Cetto and Escandón-Rivera. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Adolfo Andrade-Cetto, YWFjQGNpZW5jaWFzLnVuYW0ubXg=