Anti-diabetic formulations of Nāga bhasma (lead calx): A brief review

Abstract

Introduction:

Ayurvedic formulations usually contain ingredients of herbal, mineral, metal or animal in origin. Nāga bhasma (lead calx) is a potent metallic formulation mainly indicated in the treatment of Prameha (~diabetes). Until date, no published information is available in compiled form on the formulations containing Nāga bhasma as an ingredient, their dose and indications. Therefore, in the present study, an attempt has been made to compile various formulations of Nāga bhasma indicated in treating Prameha.

Aim:

The present work aims to collect information on various formulations of Nāga bhasma mainly indicated in treating Prameha and to elaborate the safety and efficacy of Nāga bhasma as a Pramehaghna (antidiabetic) drug.

Materials and Methods

Critical review of formulations of Nāga bhasma is compiled from various Ayurvedic texts and the therapeutic efficacy of Nāga bhasma is discussed on the basis of available data.

Result and Conclusion:

Antidiabetic formulations of Nāga bhasma were discovered around 12^th century CE. There are 44 formulations of Nāga bhasma mainly indicated for Prameha. Haridrā (Curcuma longa Linn), Āmalakī (Emblica officinalis), Guḍūci (Tinospora cordifolia) and Madhu (honey) enhance the antidiabetic action of Nāga bhasma and also help to prevent diabetic complications as well as any untoward effects of Nāga bhasma. On the basis of the reviewed research, it is concluded that Nāga bhasma possesses significant antidiabetic property.

INTRODUCTION

Ayurvedic system of medicine recognizes the importance of metals in treating different ailments. Ayurveda utilizes metallic preparations in the form of “Bhasma” (metallic preparations in calx form). Bhasma are the product of repeated calcination of metals in herbal extract or juice media. These metallic preparations occupy a significant place in Ayurvedic pharmacopoeia. The well-known metals frequently used in Ayurveda include Pārada (mercury), Svarṇa (gold), Rajata (silver), Tāmra (copper), Loha (iron), Nāga (lead) and Vaṅga (tin). Bhasma are considered highly potent and effective medicines even at small dosages.[1] Due to their high potency, bhasmas are rarely used in solitary form. To facilitate the dose administration, to avoid any untoward effect and to enable other beneficial effects of herbal drugs bhasma are mostly given in formulation forms by combining with many herbal drugs.

Diabetes comprises a group of common metabolic disorders that share the phenotype of hyperglycemia. With an increasing incidence worldwide, Diabetes is likely to continue to be a leading cause of morbidity and mortality in the near future. Herbo-mineral drugs of Ayurveda having potential of decreasing blood sugar levels have been tested in experimental animal models and found effective. Nāga bhasma is a well-known preparation frequently used in the treatment of various systemic diseases specially Prameha (diabetes) and is familiar as Pramehakarikesarī.[2] It is suggested that the Bhasma in combination with other herbs are devoid of any untoward effects.[3] Here an attempt has been made to collect data pertaining to different antidiabetic formulations of Nāga bhasma. Modern science considers lead and lead compounds as toxic to human health. The manifestation of extraordinary medicinal properties in Nāga bhasma indicates that the Ayurvedic processes involved in its preparation must be bringing about radical changes in the properties of lead which not only destroy its toxic nature but also impart to its extraordinary medicinal properties as described in the Ayurveda classics. For this reason research works on toxicity studies and Pramehaghna (antidiabetic) effect of Nāga bhasma are compiled in the present work to highlight its safety and efficacy.

BACKGROUND

Internal use of Nāga is first found mentioned in Caraka Saṃhitā.[4] Rasendra Mangala (8^th century CE) is the second treatise in which two formulation of Nāga as Sarvanetrarogahara Kalpa[5] and Vajrāṅga Sundarī guṭī[6] advised internally. Ānandakanda (12^th century CE) is the first treatise in which the properties[7] of Nāga such as Atyuṣṇa (hot for internal use) Tikta (bitter taste), Vāta-kaphahara (reduces Vātaand Kapha) Pramehaghna (antidiabetic), Dīpana (appetizer) and Āmavātanut (effective in rheumatoid arthritis) are described. Rasaratnasamuccaya (RRS) (13^th century CE), a well-known comprehensive treatise of Ayurveda documents the use of Nāga bhasma in treating diabetes. Later on, many texts emphasize the antidiabetic property of Nāga bhasma. Recent research works also proves anti-hyperglycemic effect of Nāga bhasma.

MATERIALS AND METHODS

Thirty-five classical texts have been studied and various formulations of Nāga bhasma are compiled from texts of Rasashāstra including Rasendracūḍāmani (RChu) (12^th century CE), RRS (13^th century CE), Rasendrachintamani (13^th century CE), Rasendrasārasamgraha (14^th century CE), Rasakāmadhenu (17^th century CE), Yogaratnākara (18^th century CE), Bhaiśajya Ratnāvali (19^th century AD), and Bṛhatrasarājasundara (19^th century CE). All formulations which contain Nāga bhasma and mainly or secondarily indicated as antidiabetic are included in this study. Of 35 texts, only eight texts which are described above have mentioned antidiabetic formulations of Nāga bhasma. (Tables 1 and 2) Percentages of Nāga bhasma are calculated by considering all herbal, metallic and mineral ingredients. Percentages are not calculated if the preparation of formulation involves multiple procedures. Dose per mg per day is calculated on the basis of percentage of Nāga bhasma and dose given in classical text. Most of the formulations contain many herbal ingredients hence only metallic and mineral ingredients are mentioned in tables. The metallic ingredients are given to facilitate the future research on the combined effect of more than one bhasma. This study is related with formulations of Nāga bhasma hence Nāga bhasma is not mentioned in metallic ingredient content of all formulations. The dose is given as mentioned in the classics; however dose is not given where it is not mentioned in classical text. Name of some formulations are repeated in table because they are mentioned in more than one classical text with some difference either in one or more ingredient or differ in method of preparation. The metallic and mineral ingredients in every formulation are in calcined form except Pārada, Gandhaka, Hāratāla, Manaḥśilā, Rasasindhūra, Ṭankaṇa, Śilajatuand Hiṅgula. Published research works by various journals on Nāga bhasma which are available on the internet are also compiled.

Table 1.

Nāga formulations mainly indicated as antidiabetic

Table 2.

Nāga formulations secondarily indicated as antidiabetic

Research work on Nāga bhasma

In an acute toxicity study of Nāga bhasmaat 160 therapeutic equivalent dose (TED) level was found to be safe, while no toxic effect was observed in chronic toxicity study at 5 TED level. This study also shows that Nāga bhasma prepared by Paradand Manaḥaśilā media significantly reduces blood sugar level.[8] A sense of well-being was reported by 90% patients and 65% of the patients showed a reduction in blood sugar, who were consuming modern antidiabetic drug along with Nāga bhasma; while, 50% of patients who were on only Ṣaṣtipuṭa Nāga bhasma also showed a reduction in blood sugar levels. This study can prove to be a lead toward addition of the Bhasma as an adjuvant to the synthetic drugs for the management of diabetes mellitus.[9] In a testicular regenerative potential study of Nāga bhasma, it was observed that the test drug when given simultaneously with CdCl2 (cadmium chloride) showed marked prevention of testicular degenerative effects of CdCl2 and when given alone after 36 h of CdCl2 administration, showed a noticeable regenerative potential on partially degenerated testis. Nāga bhasma showed specific regenerative effect on germinal epithelium of testis. CdCl2 is toxic to testicular germinal epithelium and its effects can be minimized by Nāga bhasma. At higher doses, the drug is found very effective, thus these findings are well collaborated with the Ayurvedic concept of Vṛṣya property of Nāga bhasma.[10]

DISCUSSION

From literary study, it is clear that metals and minerals were well-known from Saṃhitā period,[11] but their internal use was very limited. The use of metals/minerals for rejuvenation and other purposes started from 8^th century CE. Acārya Caraka has mentioned a formula “Muktādya cūrna” which contains Sīsaka chūrṇa (powder of Nāga. It is understood that in Caraka Saṃhitā, metals and minerals are used in the form of powder of oxides obtained by repeated cycles of heating metals and minerals followed by quenching in cow urine, Triphalākvāthaetc, which is known as Ayaskṛti. The process of Ayaskṛti is nearly similar to the purification procedure of metals and minerals mentioned in Rasashāstra except that number of quenching and media described for purification are different. Therefore it can be concluded that Caraka utilized metals/minerals in Śodhita (purified) form and the powder of Nāga mentioned in Muktādya cūrna is a mixture of organic compounds from media used for Ayaskrti and red oxide of lead (PbO).

Suśruta and Vāgbhaṭa[12,13] prescribe the use of Nāga for local application in eye disease but not internally. Suśruta categorizes Nāga under Trapvādi gana (group of tin) and is the first who mention its utility in eye diseases.[14] Dalhana mentions the corrosive property of Nāga and advised its use in treating eye diseases like Abhiśyanda (conjunctivitis).[15] Suśruta prescribes the use of powders of metals and minerals prepared by pounding. It is difficult to convert some metals such as Nāga, Svarṇa (gold) and Rajata (silver) into a fine powder by merely pounding due to their highly malleable nature. Hence, it can be considered that Suśruta also employed Ayaskriti method for powdering of metals/minerals. Bhasmas are safer than powder of metals. Therefore, it is advisable to use bhasma of respective metals and minerals instead of their powders while preparing formulations as per Suśruta Saṃhitā. Further research is required to evaluate this claim.

After Caraka Saṃhitā; the internal use of Nāga is found mentioned in Rasendra Maṅgala. The author mentions 2 formulations containing Nāga as an ingredient for treatment of eye diseases and 4 formulations for Dehavāda. The author also describes antidiabetic property of Nāga but has not mentioned any antidiabetic formulation. This indicates that Nāga was mostly utilized for Lohavāda purpose up to 8^th century CE and its therapeutic use was very limited. It is believable that after the decline of the knowledge of the process of Lohavāda, after people failed to achieve success in this field, they reutilized the drugs used in Lohavāda for the treatment of common diseases to recoup the loss. Many formulations were discovered after finding miraculous therapeutic effect of these drugs. This evolution in the field of Rasashāstra took place between the period 8^th and 12^th centuries CE. It can be assumed that from Rasendra Maṅgala onwards the ancient scholars gradually came to know different properties of Nāga and in 12^th century CE they discovered many antidiabetic formulations of Nāga.

Rasendrachūḍāmaṇi mentions three antidiabetic formulations which contain up to 50% Nāga bhasma. Maximum percentage of Nāga bhasma (100%) is observed in Nāga bhasma Yoga[16] and Nāgādi Yoga.[17] These two preparations contain only Nāga bhasmaas an ingredient and administration was advised along with Haridra churna (powder of Curcuma longa Linn), Āmalakī cūrna (powder of Emblica officinalis Gaertn) and Madhuas vehicle. Lowest proportion of Nāga bhasma is found in 5^th Loha kalpa[18] that contain 99 parts Triphalā churna and one part Nāga bhasma. In the remaining formulations, percentage of Nāga bhasma ranges from 4.54% to 50.00%. It can be supposed that if one decides to administer any one formulation mentioned above at the dose 125 mg/kg then in one dose, the formulation would contain 62.5-125 mg/kg Nāga bhasma. In pharmacological research works of acute and chronic toxicity study such as “comparative study of some commercial samples of Nāga bhasma” conducted at National Chemical Laboratory, have established safety criteria of Nāga bhasma, the dose administered therein was higher (up to 225 mg/kg) than the percentage of Nāga bhasma in above formulations.[8] Therefore, it can be assumed that these formulations are safe at the dosage mentioned in classics except six formulations in which dose ranges from 250 to 666 mg/day. Furthermore due to change in pharmacokinetic and pharmacodynamic action of drug in combination form, the safety of these formulations needs to be established.

A total of 67 antidiabetic formulations are found in eight classical texts mentioned here previously. Out of them, 44 are mainly indicated for diabetes while remaining 23 formulations are primarily indicated for diseases like Rājayakṣmā (tuberculosis), Kuṣṭha (skin diseases), Vātavyādhi (diseases of Vāta), Hṛdayaroga (diseases of heart) and secondarily indicated for Prameha. It can be estimated that these 23 formulations may be useful when Prameha is associated with other diseases, i. e., in the stage of Vyādhisaṅkara. Only three formulations are found indicated in specific type of Pramehaviz Vedavidyā vaṭi[19] for Ikṣumeha (glycosuria), Nāgabhaktyādi yoga[20] for Surāmeha (phosphaturia) and Vidyāvāgīśarasa[21] for Lālāmeha (albuminuria). Until date, no research work is found on these specifically indicated formulations. However, it will be a great contribution in the field of Ayurveda if research were to be conducted on Nāga bhasma formulations specifically indicated for diabetes. Properties of Nāga bhasma includes Uṣṇa Vīrya (hot in action), Tikta Rasa (bitter taste), cures Vātaja-Kaphaja Prameha and Udakameha (polyuria).[22] Thus it is recommended that Nāga bhasmacan be used in Vātaja and Kaphaja Prameha. However no text has mentioned contraindication of Nāga bhasmain Pittaja Prameha therefore for better safety, it can be assumed that Nāga bhasma should be used cautiously in Pittaja Prameha.

There are 33 antidiabetic preparations of Nāga bhasma which contain Pārada and Gandhaka along with other metallic/mineral ingredients and 18 preparations with Rasasindhūra. Pārada possesses Yogavāhi property,[23] which makes it ideal to combine with other metals/minerals to increase their potency and therapeutic efficacy. Rasasindhūra is a sublimated product of Pārada and Gandhaka and also possesses antidiabetic property.[24] This may be the reason behind making combined formulations of Nāga bhasma with Pārada, Gandhaka and Rasasindhūra. In manyformulations, Haridrā, Amalakī, Guḍūciand Madhu are taken as ingredients and also advised as vehicles. In an in vitro study, it was observed that Haridrā significantly suppressed increased blood glucose. The extract stimulated human adipocyte differentiation in a dose-dependent manner and showed human peroxisome proliferator-activated receptor-gamma ligand-binding activity which is useful in the treatment of dyslipidaemia and hyperglycemia.[25,26] These results indicate that Haridrāis a promising vehicle for the prevention and amelioration of type 2 diabetes.[27] Vāgbhaṭa says that Haridrāis superior among those which cure Prameha.[28] Haridrā is also mentioned in Viṣaghna Gaṇa[29] and is a drug used in śodhanaof Nāga.[30]

It has been found that consumption of natural honey reduces cardiovascular risk factors, particularly in subjects with elevated risk factors.[31] Use of honey can also help avoid hypoglycemic shock with antidiabetic preparations. Ghee is resistant to free radical damage and is lactose free. Scientific studies have indicated the ability of ghee in supporting physical and mental performance. Ghee also acts as anti-ageing, nutritive for nerves and brain cells.[32] Āmalakīis mentioned in Agryasaṅgraha as drug superior among those which prevent ageing process.[33] Anti-ageing effect is correlated with free radical and anti-oxidant activities which are expected in treating diabetes. Āmalakī is an ingredient in Triphalā and according to a study, oral administration of the extract of Triphalā help to reduce the blood sugar level.[34] Guḍūci also possesses potent antidiabetic activity that reduces blood sugar level.[35] Guḍūci also has antioxidant activity[36] and use of antioxidants reduces oxidative stress and alleviates diabetic complications.[37] Thus, it can be assumed that use of Haridrā, Āmalakī, Guḍūci and Madhu as vehicles along with antidiabetic formulations of Nāga bhasma is helpful in enhancing its efficacy and also in avoiding diabetic complications.

Toxicity and antidiabetic studies mentioned previously have given the safety profile of Nāga bhasma. A comparative study of some representative samples of Nāga bhasma from chemical and structural point of view showed that the Nāga bhasma samples were predominantly crystalline, i.e., mixture of PbO Pb3O4.[38] Other work on synthesis, characterization and histopathological study of Nāga bhasma showed that Nāga bhasma is nontoxic (6 mg/100 g/day), while crude lead (6 mg/100 g/day) is highly toxic.[39] Thus it appears that in bhasmīkaraṇa process (calcination using herbs) the crude lead is converted into Nāga bhasma, which is found to be nontoxic at lower dosages. Conversion of Ayurvedic measurement of dose into modern dose is given in appendix 1. In the present study, the information obtained on various formulations of Nāga bhasma mainly indicated for diabetes is compiled and safety of Nāga bhasma is highlighted. Probable logic behind various ingredients in antidaibetic formulations of Nāga bhasma and advised vehicles is also discussed in detail. This work provides many formulations to treat diabetes and hence may be helpful for further research on antidiabetic formulations of Nāga bhasma.

CONCLUSION

There are 44 formulations of Nāga bhasma mainly indicated for Prameha. According to the properties of Nāga bhasma, it is mainly useful in Vātaja-Kaphaja Prameha and should be used cautiously in Pittaja type of Prameha. Haridrā, Āmalakī, Guḍūci and Madhu enhance the antidiabetic action of Nāga bhasma and also are helpful in preventing diabetic complications. On the basis of previous research, it is concluded that Nāga bhasma possesses significant antidiabetic property and is a safe drug. Most of the formulations of Nāga bhasma are not available in the market and no research work has been performed on the safety of these formulations. Thus, there is an urgent need to conduct research on safety and efficacy of antidiabetic formulations of Nāga bhasma.

APPENDIX 1

Māṣa = 1 g, Ratti = 125 mg, Tola = 12 g, Valla = 375 mg, equal to 1 horse g = 250 mg, equal to badarāphala = 500 mg, Karṣa = 12 g