Golden Pen Award | Research Progress on the Functions and Pharmacology of Common Mineral Drugs

Mineral medicine is one of the essential components of traditional Chinese medicine and plays a significant role in clinical applications. Mineral medicine has a long history of application in China, with 134 types listed in the Compendium of Materia Medica alone, including 28 types of metals, 14 types of jade, 72 types of stones, and 20 types of halides (minerals soluble in water). The modern edition of the Chinese Pharmacopoeia in 2015 included 25 types of mineral medicine, and the newly revised edition in 2020 also contained dozens of mineral medicinal materials. Based on different compositions, mineral medicine can be divided into metallic mineral medicine and non-metallic mineral medicine.

1. Iron-containing Mineral Medicine and Its Compounds

Iron is the most abundant and crucial element for hematopoiesis in the human body. There are over 20 types of iron-containing mineral medicine, including iron, iron filings, iron oxide powder, Yuliang (a kind of mineral medicine), lodestone, green vitriol, cinnabar, native copper, etc. Additionally, iron is also present in various other mineral medicines such as Posuo Stone, Qingmeng Stone, Red Halloysite, Calamine, Fulonggan (a type of earth used medicinally), and Dragon Bone. Besides its elemental form, iron mainly exists in minerals in the form of oxides, sulfides, or sulfates. Most iron-containing mineral medicines have a sweet and salty taste, are cool or neutral in nature, non-toxic, and are attributed to the Heart, Liver, and Kidney meridians. They primarily calm the mind, dispel wind pathogens, nourish blood and qi, soothe the liver and reduce adverse qi flow, treat traumatic injuries, and promote tissue regeneration. Iron-containing mineral medicine and its compounds are clinically used to treat various conditions such as epilepsy, swelling and toxicity, iron-deficiency anemia, and blood deficiency or insufficiency caused by various reasons.

Modern pharmacological research has shown that iron deficiency can lead to metabolic dysfunction, decreased immune function, emotional irritability, sluggish response, delayed growth and development, fetal malformations, preterm birth, stillbirth, postpartum relaxation bleeding, and other symptoms. Daizhe Stone (haematite) contains essential elements for the human body such as iron, silicon, aluminum, and calcium, and has pharmacological effects such as sedation, anti-inflammation, anti-convulsion, and hemostasis. After being taken internally, iron-based mineral medicine is converted into ferrous salts that are easily absorbed and utilized under the action of gastric acid. They can provide Fe2+ required for the synthesis of hemoglobin and stimulate the regeneration of red blood cells. In addition, Fe2+ is an important cofactor in the synthesis and maturation of collagen at bone injury sites, playing a crucial role. Fe2+ can also promote the proliferation of reticulocytes in the bone marrow and surrounding blood at fracture sites, thus having the effect of nourishing blood and qi, and strengthening bones and muscles.

2.Copper-containing Mineral Medicine and Its Compounds

Mineral medicines containing copper mainly include purple copper ore, copper verdigris, copper ore, stone gall, kongqing (a type of mineral pigment), zengqing (another type of mineral pigment), green salt, and over 10 other types. Besides its elemental form, copper mainly exists in minerals in the form of basic copper carbonate, copper oxide, copper acetate, or copper sulfides. Copper-containing mineral medicines generally have a sweet, bitter, or sour taste, and are cool, neutral, non-toxic, or slightly toxic. Their main effects include treating fractures and injuries, promoting blood circulation, breaking down hard masses, stabilizing qi deficiency, clearing the lungs of phlegm, nourishing the liver and improving vision, replenishing injuries, promoting healing, and dissipating blood stasis and swelling.

Copper is one of the essential trace elements in the body, having a certain degree of influence on the cardiovascular system, bones, the central nervous system, and the production of red blood cells. The therapeutic effects of copper-containing mineral medicine are mainly reflected in promoting blood circulation and dispelling blood stasis, removing necrotic tissue and promoting regeneration, and relieving spasms and pain. For example, copper verdigris is often used to treat traumatic injuries, malignant sores, and skin ulcers, showing good therapeutic effects in the clinical treatment of skin and mucosal suppurative inflammation. It has a strong inhibitory effect on various Gram-positive cocci such as Staphylococcus aureus and Staphylococcus epidermidis. Another example is the clinical use of natural copper combined with other herbs to treat nonunion of bone after femoral shaft fracture with spleen and kidney deficiency and blood stasis, which has the effect of nourishing the spleen and kidneys, promoting bone healing, and activating blood circulation.

Modern pharmacology indicates that Cu2+ is crucial for maintaining normal hematopoiesis and the health of the central nervous system. Research reports show that Cu2+ can be located in the active centers of various enzymes, participating in the synthesis of cytochrome C, tyrosinase, ascorbic acid oxidase, and galactose oxidase, and regulating body metabolism by influencing enzyme activity. Copper-based drugs are important for bone healing and fracture repair because Cu2+ exists in the active sites of enzymes in the form of metalloenzymes during the healing process, promoting the formation of covalent bonds between bone collagen protein and elastin, enhancing the toughness of collagen fibers and increasing the insolubility of collagen, thereby increasing bone strength. Stress stimulation also promotes the formation of new bone, which is closely related to the formation of bone callus. In addition, literature reports indicate that Cu2+ can induce angiogenesis by upregulating several angiogenic genes, and can also promote the transformation of target cells into osteoblasts by promoting the remodeling of the extracellular matrix.

3.Calcium and its compound mineral drugs

Calcium mineral drugs mainly contain oxides, carbonates, calcium fluoride, and other active ingredients, including 13 types of mineral drugs such as marble, limestone, dragon bone (fossilized animal bones), huirui stone (a type of mineral with medicinal properties), gypsum, rock silkworm, rock swallow, amethyst, and so on. Calcium ions in calcium mineral drugs are of great significance to human physiological functions. They form soluble calcium salts under the action of gastric acid, which have important impacts on the permeability of capillaries and cell membranes, the excitability of nerve cells, muscle contraction, and the coagulation process. Research shows that the mechanism of huirui stone treating prolonged menstrual bleeding may be through increasing the calcium content in the blood, not only acting as a procoagulant but also reducing the permeability of blood vessel walls, thereby achieving the purpose of hemostasis. The Ca2+ in amethyst can affect the expression of follicle-stimulating hormone, luteinizing hormone, follicle-stimulating hormone receptor, luteinizing hormone receptor, and other factors in local ovarian tissue, thus improving ovulation disorders. In addition, as an essential element for the human body, calcium is the main inorganic component of bones and teeth, and it can also promote the activity of certain enzymes in the body, regulate enzyme activity, participate in nerve and muscle activities and neurotransmitter release, and regulate hormone secretion.

Calcium mineral drugs are mostly pungent, sweet, and sour in taste, with a warm or neutral nature, and are non-toxic. They are mainly used to replenish qi and nourish deficiencies, stop bleeding from traumatic injuries, treat all types of blood loss, and alleviate blood pressure drops in women. Therefore, calcium mineral drugs have extensive clinical applications in gynecological diseases. The calming and soothing effect of calcium mineral drugs is an important function of this class of drugs. Clinically, they are mainly used for treating convulsions, epilepsy, and mania, such as the Guizhi Jia Longgu Muli Tang (a traditional Chinese medicine formula combining cinnamon twig, dragon bone, and oyster shell) and Chaihu Jia Longgu Muli Tang (a traditional Chinese medicine formula combining bupleurum root, dragon bone, and oyster shell) in the Treatise on Cold Damage Diseases (Shang Han Lun), which are primarily used for calming frightened patients.

4.Sodium and Its Compound Mineral Drugs

Common mineral drugs containing sodium salts mainly include mirabilite, table salt, xuanmingfen (refined salt), and borax. Sodium-containing mineral drugs are mostly salty, bitter, pungent, and cold in taste, and are non-toxic. They are primarily used to treat accumulations in the five organs, alleviate heart heat and irritation, dispel evil qi, break up clotted blood, dissipate heat and promote bowel movements, soften hard masses and dissipate nodules, clear heat and detoxify, expel phlegm from the chest, and benefit bowel and urine excretion as well as menstrual flow.

Mirabilite, mainly composed of sodium sulfate, has three main applications throughout history: eliminating excess heat, cleansing intestinal residue, and breaking up hardened masses of heat. It is suitable for promoting blood circulation and intestinal movement. In modern clinical practice, mirabilite is used to reduce local leukocyte infiltration, regulate immune function, and prevent and treat post-surgical incision infections. It has the effect of clearing heat, purging fire, and softening hard masses. Mirabilite can also stimulate the reticuloendothelial system of the spleen and appendix, enhancing their phagocytic function and improving the body's resistance to disease. Modern pharmacological mechanisms show that mirabilite has a hyperosmotic effect that absorbs water. When applied externally to wounds, it can absorb exudate around the wound, reduce the permeability of capillaries, thereby achieving the effect of reducing swelling and keeping the wound dry. At the same time, mirabilite can promote the phagocytic ability of the reticuloendothelial system. By stimulating nerve reflexes, it promotes local blood circulation, accelerates lymphocyte production, and has anti-inflammatory and analgesic effects. Therefore, external application can effectively promote wound healing.

5.Other Light Metal Mineral Drugs

Other light metal mineral drugs include zinc-containing calamine, manganese-containing unnamed minerals, magnesium-containing cold water stone, and aluminum-containing alum. Calamine is a calcined and quenched product of smithsonite and hydrozincite, with zinc carbonate as its main component. It has the effect of absorbing moisture, relieving itching, and healing sores. To this day, it is commonly used in dermatology for astringency, sterilization, and itching relief, treating skin itching, wound infections, and other conditions. Zn2+ is the key to its antibacterial effect, which can destroy the respiratory system of bacteria and inhibit their reproduction and proliferation abilities.

"Unnamed Heterogeneous" is a manganese-containing mineral drug that has the effects of removing blood stasis and stopping bleeding, reducing swelling and relieving pain, and promoting muscle regeneration and wound healing. Clinically, it can be used to treat traumatic injuries, bleeding from cuts and wounds, and abscesses and sores. Modern pharmacological research shows that manganese is a component of the body's transaminases and proline peptidases, participating in the process of oxidative phosphorylation in the human body. It has an antagonistic effect against thiamine and is involved in hematopoiesis and fat metabolism.

Alum is a crystal processed and refined from the mineral alunite, with the main chemical component of potassium aluminum sulfate dodecahydrate. It has the effects of eliminating phlegm and dampness, detoxifying and killing insects, stopping bleeding, and relieving diarrhea. Clinically, it is used externally to dry dampness and relieve itching, such as in the treatment of eczema, and internally for prolonged diarrhea, rectal bleeding, uterine bleeding, and epileptic mania. The detoxifying and insecticidal effect of aluminum-containing mineral drugs is due to the ability of aluminum ions to bind with ATP to form stable complexes, inhibiting energy flow within cells, especially the ATP proton transport on membranes, leading to energy deficiency and ultimately reducing bacterial motility. Additionally, aluminum ions can deplete ATP in nerve cells that serve as excitatory neurotransmitters, further inhibiting synaptic activity, which is the mechanism of action of aluminum-containing mineral drugs in treating epileptic mania.

6.Heavy Metal Mineral Drugs

Heavy metal mineral drugs include mercury-containing substances such as mercury, cinnabar, spirit sand, red powder, and powdered frost, lead-containing substances such as lead powder, lead oxide, lead frost, black tin dan, mituo monk, and zimuxuan, gold-containing substances such as gold dust, gold foil, gold stone, and gold top, and silver-containing substances such as silver dust, silver foil, silver paste, raw silver, yellow silver, black silver, and cinnabar silver. Most heavy metal mineral drugs have a pungent, salty, cold, and toxic taste. They primarily have the effects of calming the spirit, nourishing the five organs, replenishing essence and marrow, regulating blood flow, removing decay and promoting tissue regeneration, treating sores and detoxifying, and treating skin diseases such as ringworm and scabies. Chinese medicines containing lead and mercury are often used to treat conditions such as damp sores, ringworm, scalds, burns, ulcers, or chronic diarrhea. For example, lead oxide, a lead-containing mineral drug, can directly kill bacteria and parasites, and can be used externally to treat eczema, ringworm, sores in the mouth and tongue, etc. Modern pharmacological research has clarified the pharmacological effects of mercury-containing mineral drugs. Hg2+ can precipitate proteins and generate denatured protein salt precipitates with proteins in local tissues of the body, thus producing varying degrees of astringent and hardening effects.

7.Non-metallic Mineral Drugs

Non-metallic mineral drugs include sulfur-containing sulfur and arsenic-containing realgar. The main component of sulfur is sulfur, which has strong insecticidal and anti-itching effects. However, excessive intake can easily lead to the formation of hydrogen sulfide and sulfides in the intestine. When absorbed into the blood, they form sulfhemoglobin with hemoglobin, causing tissue hypoxia and leading to central paralysis and death. Therefore, excessive or prolonged use is not recommended. The main chemical component of realgar is As2S2 (or As4S4), which also contains a small amount of soluble arsenic (As2O3) and other inorganic mineral elements. It is a toxic mineral drug, and its toxicity is related to arsenic.

Although mineral drugs have clear clinical effects, safety issues remain a key limitation to their clinical application. For example, lead-containing mineral drugs are toxic to the nervous, cardiovascular, and renal systems, and their toxicity is not only related to the drug dosage but also to the valence state and bioavailability of heavy metal elements. Numerous studies have shown that excessive accumulation of aluminum in the body can cause severe neurotoxicity and affect cognitive and memory functions. Therefore, the therapeutic dosage of aluminum-containing mineral drugs should be strictly controlled. Additionally, processing or combination with other herbs is an effective means to reduce the toxicity of heavy metal mineral drugs. For instance, the toxic substance content in cinnabar is significantly reduced after water-flying processing, and the combination of licorice root, skullcap, and rhubarb in Niuhuang Jiedu Pian (cow-bezoar detoxifying tablets) with realgar has a detoxifying effect, reducing the hepatotoxicity, nephrotoxicity, and genetic toxicity of realgar.

References:

[1] Xu Shan, Xu Liu, Xiang Tangyong, et al. Research Progress of Metal Mineral Drugs [J]. Journal of Nanjing University of Chinese Medicine, 2021, 37(05): 778-785.

[2] Yang Hui. Function and Research Progress of Common Non-metallic Mineral Drugs [J]. China Non-Metallic Minerals Industry Guide, 2022, (04): 1-3+7.

[3] Ye Hongbo, Lv Guangfu, Ma Chao, et al. Research Progress on Pharmacological Effects of Mineral Drugs [J]. Jilin Journal of Traditional Chinese Medicine, 2021, 41(05): 697-700.

About the Author

Xiaomichong, a pharmaceutical quality researcher, has been committed to pharmaceutical quality research and drug analysis method validation for a long time. Currently employed by a large domestic pharmaceutical research and development company, she is engaged in drug inspection and analysis as well as method validation.