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The purpose of this study was to review the pharmacognostic characteristics of Sasang type-specific medical herbs and suggest biological mechanisms that might be related to the personalized treatment of the East.
Major compounds and their pharmacological activities of medical herbs for each Sasang types were systematically reviewed. The pharmacognostic characteristics of its main compounds were systematically analyzed with previous studies and three web-based databases.
Sasang type-specific medical herbs were selected, and biological effects of their phytochemicals were reviewed from the pathophysiological features of each Sasang types. Phenolics were dominant in Tae-Yang type-specific herbs, iridoids and triterpenes with antipyretic and diuretic effects were in So-Yang type-specific, saponins (triterpene saponins and steroidal saponins) with antitussive effects were in Tae-Eum type-specific, and monoterpene and sesquiterpenes with stomachic effect were in So-Eum type-specific herbs.
Pharmacognostic understandings on Sasang type-specific medical herbs with consideration of type-specific pathophysiological features were provided for the first time. This study would contribute to in-depth understandings on the pathophysiology of Sasang typology and integration of East-Asian and Western personalized medicine.
Personalized medicine for improving efficacy and safety has been a major topic of medicine for thousands of years1, 2, 3 since four humoral types of Hippocrates and Galen4 and five phase and Yin-Yang based typology of traditional East-Asian medicine;2 however, those were just a coarse draft without details for pathophysiology, diagnostics, and type-specific medical treatments.
The Sasang typology is a person-centered personalized medicine dividing people into four Sasang types of Tae-Yang (TY), So-Yang (SY), Tae-Eum (TE), and So-Eum (SE) by Jema Lee in his book, Longevity and Life Preservation of the Eastern Medicine (1894, 1900);5 this book provides type-specific guideline for safe and effective medical herbs and acupuncture treatment.1, 6 It is a reinterpretation of traditional East-Asian medicine based on biopsychosocial traits with the support of thousand years of clinical experience and Confucius personality studies in Korea.1, 6, 7
There have been extensive Sasang typology studies on psychological traits,8 physical characteristics,9, 10 genetic,3 and clinical9, 11 standpoints. As for the psychological perspectives, Eysenck’s extraversion,12 Gray’s behavioral activation and inhibition system (BAS and BIS),13 Cloninger’s novelty seeking (NS) and harm avoidance (HA),14 and Chae’s Sasang personality questionnaire (SPQ)7, 8 were reported to be useful for describing each Sasang types, and the SY Sasang type has high Extraversion, high BAS and low BIS, high NS and low HA, and high SPQ; however, the SE Sasang type is on the contrary. The obesity-related body mass index (BMI) and thyroid hormonal activity-related ponderal index (PI) were reported be valuable for physical characteristics, and the TE Sasang type has high BMI and PI, whereas the SE Sasang type has low BMI and PI.1, 7, 9, 10.
As for the biological mechanism for Sasang typology, autonomic reactivity11 including hypothalamus–pituitary gland–adrenal axis reactivity10 was suggested. The sympathetic reactivity increases with the order of TE, SY, SE, and TY, and the parasympathetic reactivity decreases with the same order. Along with these, the TE Sasang type reportedly has a higher prevalence of hypertension, diabetes, obesity, and metabolic diseases, and the SE Sasang type is associated with diseases from anxiety and emotional instability.9, 12, 15
Additionally, the pathophysiological symptoms are pivotal pattern identification system for Sasang typology, and the Sasang Digestive Function Inventory (SDFI) was reported to be clinically useful for discriminating the TE and SE Sasang types.15 The SDFI measures the sturdiness of digestive system and its function and negatively correlates with functional dyspepsia.15
However, studies on mechanism of Sasang type-specific treatments were not sufficient even with proven clinical usefulness16, 17, 18, 19, 20 because the study on pathophysiological predispositions of each Sasang types11 and clinical study with complex herbal compound require sophisticated and tedious step-by-step approach.
Therefore, this study would review pharmacognostic characteristics of Sasang type-specific medical herbs which would provide physical, chemical, biochemical, and biological properties of herbal medicine with natural origin;21, 22 this would provide robust theoretical background for studying the mechanism of Sasang type-specific treatments.
The term pharmacognosy is derived from two Greek words “pharmakon” and “gnosis” which mean drug and to acknowledge, and it approaches medicinal herbs with their major constituents of phenolics, alkaloids, and terpenoids as secondary metabolites or phytochemicals.23 With the development of modern technology of extraction, isolation, purification, and diagnostic methods, lead compounds from plants contributed to the development of modern drugs24 such as aspirin from salicylic acid.25 We would evaluate previous studies7, 14, 26, 27, 28, 29, 30 regarding Sasang type-specific medical herbs and systematically review their major compounds and phytochemicals and its pharmacognostic activities with the help of previous studies and web-based databases.31, 32, 33.
This study would provide an understanding on Sasang type-specific medication from pharmacological perspectives and foundation for the integration of Eastern and Western personalized medicine in the near future.
Frequently used type-specific medical herbs of Sasang typology were selected with Longevity and Life Preservation in Eastern Medicine and Dong-Mu-Yoo-Go Yak-Sung-Ga. Their pharmacognostic features were reviewed with textbooks of herbal medicine, three web-based databases, and previous studies.26, 34. Three databases included Up-to-date of Pharmacognosy,31 Pharmacological function of traditional medical herbs,32 and Search for Pharmacognostic Information Database.33
We systematically reviewed the pharmacological properties of Sasang type-specific medical herbs in perspectives of phytochemicals or secondary metabolites of natural plants, animals, and minerals.35 Type-specific medical herbs of each Sasang types were classified into three groups of phytochemicals of terpenoids, phenolics, and alkaloids, and the pharmacological properties of each Sasang type-specific medical herbs were investigated with previous studies on its dominant chemicals.
Plant metabolites are produced by their metabolism and classified into primary and secondary metabolites. Primary metabolites, such as carbohydrates, lipids, amino acids, and nucleic acids are crucial for the growth of plants, whereas secondary metabolites, such as alkaloids, terpenoids, and phenolics, play a defensive role against herbivores and harmful ecological environment36, 37 and exhibit pharmacological activities as main compounds of medicinal herbs.38 The phytochemicals have been used for various pharmacologic activities, such as antioxidant, antimicrobial, immunostimulant, anti-inflammatory, and anticancer,36 and can be divided into three major groups of terpenoids, phenolics, and alkaloids.38
Terpenoids have diverse groups with more than 23,000 structures, they are the biggest group in the secondary metabolites,38 and include volatile compounds to attract or expel other animals with their aroma like citronellal, thymol.36 Terpenoids use isoprene as a building block and are subdivided into monoterpenes, sesquiterpenes, diterpenes, triterpenes, tetraterpenes, polyterpenes, steroid derived from triterpenes and saponins derived from triterpenes, and steroids. Iridoids are a subclass of monoterpenes.37
Phenolic compounds, which are famous for their antioxidant property, are easily found in tea, coffee, berries, fruits, and vegetables, such as rutin, quercetin, and hesperidin.35 Their antioxidant property has been regarded to protect human beings from oxidative stress and free radical-mediated diseases.38 Phenolics have hydroxylated aromatic rings in common and could be divided into phenylpropenes, coumarins, flavones, flavanones, flavonols, flavanes, isoflavones, anthocyanins, anthraquinones, stilbenes, lignans, and tannins.
Alkaloids, derived from the word of alkaline, are one of the most active secondary metabolites described as organic basic nitrogen-containing structures,36 and some of them are neutral and weakly acid.38 Most alkaloids are toxic with bitter taste. They have a long history in medication; some of them like morphine and ephedrine exhibit strong pharmacological activities. Alkaloids contain one or several nitrogen atoms in their structures and are divided into three major groups of true alkaloids, proto alkaloids, and pseudo alkaloids.37, 39
We selected and analyzed 7 medical herbs for TY type, 22 for SY type, 26 for TE type, and 21 for SE type (Table 1). One SY type-specific drug of Gypsum fibrosum is inorganic, not from plants, and two herbs (Lycium chinense and Rehmannia glutinosa) are used as two different drugs (Lycii cortex, Lycii fructus, Rehmanniae radix, and Rehmanniae radix preparat) in SY type.
Seven TY type-specific medical herbs are divided into four phenolic drugs, one terpenoid drug, and two other drugs. Although there were few numbers of TY type-specific medical herbs for analyzing and drawing conclusion,30 their pharmacological activities might be categorized as protecting liver, boosting immune system, and reducing oxidative stresses (Table 2).
The biggest group in TY type-specific drugs is phenolics consisting of phenylpropene, flavone, lignan, and stilbene. Phenolic compounds are characterized by their antioxidant, anti-inflammatory, and other biological activities.37 Under the category of phenolics, some of the lignan compounds have hepatoprotective property (silymarin from Silybum marianum), which is used to treat chronic hepatitis and live cirrhosis.35 Stilbenes acts as phytoalexin, which is a part of defense systems protecting plants against diseases,40 and resveratrol from Vitis vinifera is one of the stilbene compounds acting as a strong antioxidant agent.39 In phenolics, hepatoprotective and immunostimulant,41, 42 antioxidant and anti-inflammatory,43 antioxidant and anti-inflammatory,37 and anti-inflammatory44 effects were exhibited.
The terpene drug of TY type-specific herbs also exhibits its hepatoprotective property. In terpenoids, ursolic acid and euscaphic acid from Chaenomelis fructus have hepatoprotective and anti-inflammatory effects.45 In other groups, amygdalin and prunasin from Pruni semen showed antitussive effect,37 and asparagine from Phragmitis rhizoma showed diuretic and antipyretic activities.39
Twenty-two SY type-specific medical herbs would be classified into 13 terpenoid drugs, 3 phenolic drugs, 3 alkaloid drugs, and 3 other drugs. Secondary metabolites of SY type-specific herbs showed antipyretic, anti-inflammatory, and diuretic properties as shown in Table 3.
The major group in SY type-specific herbs is terpenoids, and iridoids and triterpenes are dominant in this group. Triterpenes have a wide spectrum of biological activities and exhibit cytotoxic and diuretic properties with bitter tastes.35 Triterpenoid group of SY type-specific herbs are used for inflammations and arthritis for their anti-inflammatory, diuretic, and analgesic properties. In terpenoids, diaphoretic and anti-inflammatory,39 antirheumatic, analgesic, and diuretic,46, 47 hypolipidemic and diuretic,48 diuretic and stomachic,39, 49 expectorant,50, 51 diuretic and antimicrobial,33, 35 antipyretic, anti-inflammatory, and antimicrobial,32, 46 purgative,52 diuretic,50 diuretic, antitussive, and expectorant,53 anti-inflammatory and antipyretic,50 hypoglycemic, sedative, and immunostimulant,50, 54 and antioxidant and immunostimulant55 activities were reported.
In phenolics, antipyretic and antioxidant,50 analgesic, anti-inflammatory, and diuretic,39, 47 and antipyretic and analgesic31, 50 properties were reported. Coumarins are aromatic and used for anti-inflammatory, diuretic, and antimicrobial properties,37 and some of them exhibit an anticoagulant property as warfarin.35 Among secondary metabolites, iridoids, alkaloids, and coumarins exhibit strong therapeutic activities.56, 57 Iridoid compounds of harpagoside in Harpagophytum procumbens are used for infections, inflammations, and rheumatism, and some iridoids have an extremely bitter taste and used for dyspepsia and lack of appetite.37
In alkaloids, antimicrobial and antipyretic31, 32, 39, 46, 50 as well as antipyretic and hypotensive31, 46, 50 properties were found. In other groups, hemopoietic,32, 58 hepatoprotective,31, 50 and antipyretic46, 49 effects were found.
Twenty-six TE type-specific medical herbs are divided into 11 terpenoid drugs, 8 phenolic drugs, 4 alkaloid drugs, and 3 other drugs. Saponin groups (triterpene saponins and steroidal saponins) hold a dominant position and TE type-specific medical herbs showed anti-inflammatory, anti-asthmatic, and antitussive properties as shown in Table 4.
In terpenoids, saponins (triterpene saponins and steroidal saponins) hold a dominant position, and sesquiterpenes is the next. Medical herbs containing saponins are generally used for expectorant and antitussive and immunostimulant agents as platycodin in Platycodon grandiflorum.35, 59 Saponin drugs and sesquiterpene drugs in TE type-specific herbs are used as antitussive and expectorant agents. There were antitussive,39, 50 anti-inflammatory and antimicrobial,39, 46 antitussive,46, 60 anti-inflammatory and osteoprotective,32, 61 anti-inflammatory and antitussive,31, 50 sedative,32, 39 expectorant and antitussive,31, 60 antidiabetic and immunomodulatory,62 anti-asthmatic and anti-inflammatory,32, 63 antitussive and anti-inflammatory,39 and inflammatory and antimicrobial46, 60 properties in this group.
Phenolic drugs of TE type-specific herbs exhibited antitussive, sedative, anti-inflammatory, hypotensive, and anti-allergic effects. In phenolics, sedative and spasmolytic,33, 39 anti-inflammatory and anti-nociceptive,31, 50 diuretic and hypotensive,39, 64 anti-inflammatory and anti-allergic,31, 65 anti-diarrhea and cardioprotective,31, 66 purgative,31, 67 anti-asthmatic and antioxidant,46, 50 and sedative68 properties were found.
Alkaloid compounds in TE type-specific herbs exhibited metabolism regulating properties against hypertension and obesity. In alkaloids, anti-asthmatic and sympathomimetic,46, 60, 69 anti-obesity,70, 71 antihypertensive and antitussive,71, 72 and hepatoprotective and anti-obesic31 properties were shown. In other groups, anti-inflammatory and anti-asthmatic,46, 73 prophylactic,74 and anti-inflammatory and analgesic50, 75 effects were reported.
Twenty-one SE type-specific medical herbs are classified into 13 terpenoid drugs, 5 phenolic drugs, 1 alkaloid drug, and 2 other drugs. As a whole, SE type-specific medical herbs tend to have stomachic, sedative, spasmolytic, and anti-inflammatory properties as provided in Table 5.
Monoterpenes and sesquiterpenes (essential oils) are the biggest part of SE type-specific medical herbs; furthermore, they are the main constituents of essential oils exhibiting gastro-protective, sedative, spasmolytic, and antimicrobial activities37, 76 and are dominant in this group. Triterpene saponins exhibit immunostimulant and tonic properties as ginsenosides and astragalosides.
In terpenoids, sedative and spasmolytic,31, 39 antipyretic and stomachic,46, 50 stomachic and antiulcer,46, 50 diuretic and stomachic,46, 50 stomachic, anti-emetic, and spasmolytic,39, 46 sedative and anti-inflammatory,39, 77 stomachic and secretory,78 stomachic and antitumor,39, 46 purgative,32, 39 tonic and adaptogenic,31, 79 immunostimulant,31, 39, 50 anti-inflammatory and antiulcer,39 and sedative and neuroprotective80 properties were reported.
The phenolics are reported to have cardiovascular regulating properties. In phenolics, anti-emetic and antitussive,39, 81 anti-inflammatory and cardiovascular-disease-lowering,82 blood circulation-promoting and spasmolytic,46, 83 and stomachic and antioxidant39, 84 properties were reported.
In alkaloids, aconitine from Aconiti radix showed cardiotonic and analgesic effects.79 In other groups, antioxidant and anti-inflammatory85, 86 and antioxidant and antimicrobial87 properties were reported.
The Sasang typology is a unique personalized medicine of Korea and suggests type-specific guideline for safe and effective use of medical herbs;1, 27 however, outlooks of pharmacognosy based on the phytochemicals have not been applied to understand the characteristics of Sasang type-specific medical herbs.28 We summarized Sasang type-specific medical herbs (Table 1) and systematically reviewed their pharmacognostic effects (Table 2, Table 3, Table 4, Table 5) in this study.
Phenolics were dominant in the TY type-specific herbs, whereas terpenoids were prevailing in other Sasang type-specific herbs. Iridoids and triterpenes with antipyretic and diuretic effects were the foremost in SY type-specific herbs, saponins (triterpene saponins and steroidal saponins) with antitussive effects were frequent in TE type-specific herbs, and monoterpenes and sesquiterpenes with stomachic effect were frequent in SE type-specific herbs.
The pathophysiology of Sasang typology have been extensively examined, and several hypotheses might be explained with pharmacognostic outlook here.8, 9, 10, 11 The TY Sasang type was reported to have the highest sympathetic reactivity and low threshold for BAS.11 In this study, with a limited number of medical herbs, TY type-specific medical herbs have biological activities of protecting liver function, boosting immune system, and reducing oxidative stress that might be caused by the activated response to stimuli from environment (Table 2). These characteristics of TY type-specific herbs come along with their dominant compounds, such as lignans, stilbenes, and terpenes.
The SY Sasang type is an extroverted, Yang-temperament, and active person with activated BAS and strong musculoskeletal body.7, 8. In this study, secondary metabolites of SY Sasang type-specific medical herbs have strong therapeutic effects from the antipyretic, diuretic, anti-inflammatory, and anti-rheumatic properties that support elevated musculoskeletal activities of the SY type and sustain Yin functions of the body for balancing with stimulated Yang functions.11 The anti-inflammatory and diuretic activities were reported to be frequent in SY type-specific medical herbs in previous studies (Table 3).88 These features of SY type-specific herbs would be explained from their prevailing constituents of iridoids and triterpenes.
The TE Sasang type was reported to have a higher prevalence of hypertension, diabetes, obesity, and metabolic disease and a lower sympathetic activity than others.9, 12, 15 Alkaloid compounds of TE type-specific medical herbs exhibit metabolism-regulating properties against obesity and hypertension. Saponins and other terpenoids of TE type-specific medical herbs were used as antitussive and expectorant agents. Anti-inflammatory, anti-asthmatic, and antitussive properties were common in TE type-specific medical herbs as shown in Table 4. These results are in accordance with previous studies89 that the TE type-specific medical herbs have antitussive, expectorant, and diaphoretic effects and might be related with lowered sympathetic reactivity and impaired or less activated lung function, as described by Jema Lee.10, 11
The SE Sasang type is an introverted and Yin-temperament person with lean body shape from activated BIS. Furthermore, they are reported to have prolonged and elevated sympathetic reactivity that might lead to frequent problems with dyspepsia, low digestive function, and anxiety.9, 12, 15 The SE type-specific medical herbs have stomachic, sedative, spasmolytic, and anti-inflammatory properties for the dominance of monoterpene and sesquiterpene compounds (Table 5). Monoterpene and sesquiterpene compounds are constituents of essential oils, and one of the previous studies showed that the SE type-specific medical herbs are usually aromatics helping digestive dysfunction and suppressing stress-related responses.11, 15, 90
The Sasang typology is a successfully systematized traditional person-centered personalized medicine dividing people into four Sasang types and suggesting safe and effective use of medical herbs, and homeopathy might be the medical theory of European countries with same idea. Homeopathy considers a patient as a whole person with his/her typical physical, emotional, mental, constitutional, biographical, and environmental aspects91, 92 and provides type-specific description with better safety and efficacy as the Sasang typology does.93 For example, the aconitine from Aconiti radix is a SE Sasang type-specific medical herb for heating up the body and boosting digestive function, and in homeopathy, aconitine is used for treating anxiety of aconite type patients.94
However, as for the substantial differences to be acknowledged, the Sasang typology divides humans into four types depending on their psychological and pathophysiological characteristics and uses type-specific medical herbs in combination to strengthen their clinical effects. On the contrary, homeopathy labels patients with clinical responses to one specific medical drug, which resulted in tens of homeopathic types and prescribes one specific medicine only for one patient. Detailed comparison between Sasang typology and homeopathy from pharmacognostic perspectives is needed for the development of integrative personalized medicine with medical herbs.
This study might have limitations for generalization of the results since we could not fully cover the pharmacognostic effects of all the Sasang type-specific medical herbs in here for the lack of reported studies. The pharmacological effects of minor compounds of each medical herb and that of type-specific decoctions are guaranteed to be examined. The systems biology would be needed for the elucidation of pharmacological effects in Sasang typology that prescribes decoctions made with several type-specific herbs in combination. And, although the cold-hot subgroup differentiation of Sasang typology is pivotal for the clinical practice, it was not reflected in this review.
In this study, the pharmacognostic characteristics of Sasang type-specific medical herbs were systematically reviewed according to their chemical compounds and biological properties, and those were discussed with Sasang type-specific pathophysiological mechanisms for the first time. Though pharmacognostic studies on clinical effects of type-specific herbal mixture or formula is guaranteed, this study would provide foundations for pharmacology of Sasang typology and help in understanding the characteristics of Sasang type-specific herbs from the Western pharmacognostic view.
The authors have no conflicts of interest to declare.
This work was supported by a 2-year Research Grant of Pusan National University.