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Abstract

Background

Kidney-Yang deficiency is one of the common medical syndromes in traditional medicine, characterized by symptoms such as weakness, coldness in the lower back and knees, cold, fatigue, etc. In clinical practice, Yang tonifying medicines are often used to treat patients with Kidney-Yang deficiency. Moreover, the medicinal processing method according to the principles of traditional medicine can enhance the effects on the Kidney of these herbs. This brief overview aims to gather and assess the post-processing modifications to the chemical composition and the kidney-Yang tonifying effects of specific traditional herbal remedies.

Methodology

Firstly, all kidney-Yang tonifying herbs were collected. Next, the selection was made based on the herbs with processing procedures specified in Circular 30/2017/TT-BYT issued by the Vietnamese Ministry of Health. All studies on the chemical composition and/or effects of processed drugs were searched in the PubMed and Google Scholar databases using the search formula: processed + scientific name of herbal medicine. Finally, among the studies on the changes in effects after processing, only studies on the tonifying Yang effect were included in this review.

Results

The kidney Yang-nourishing effects of the five traditional herbal medicines prescribed in Circular 30/2017/TT-BYT by the Ministry of Health of Vietnam (Radix Morindae officinalis, Cortex Eucommiae, Herba Cistanches, Semen Cuscutae, and Radix Dipsaci) have been demonstrated through several studies and summarized. From the PubMed and Google Scholar databases, 25 studies were collected for the review. Additionally, the changes in composition and content of certain active compounds in these herbal medicines have also been searched and reported.

Conclusion

This report provides a brief overview of the differences between chemical constituents and kidney-Yang tonifying of some traditional herbs after processing to partially contribute scientific evidence for standardizing the preparation processes and serve as an important reference for clinical practitioners of traditional medicine.

Keywords

kidney-Yang tonifying traditional herbs processing chemical constituents Yang tonifying herbs

Introduction

The disease is a process that disrupts the balance between various factors in the body and is used to explain the causes of many pathological conditions in modern medicine, such as gastric ulcers (imbalance between protective and ulcer-causing factors), Parkinson's disease (imbalance between acetylcholine and dopamine levels in the brain), and more. Similarly, many traditional medical syndromes are believed to be a result of imbalances within the body, particularly imbalances between Yin and Yang. According to the Eight Principles (eight diagnostic principles of traditional medicine), Yin and Yang represent the overall manifestation of the syndrome and are the first factors considered in the diagnostic process.¹

In addition to Yin and Yang, the “Full-Empty” Pattern is one of the four principles in the Eight Principles. It encompasses the clinical manifestations of overall weakness and depletion of the body's vital energy (Qi). Within the category of empty patterns, kidney-Yang deficiency is one of the syndromes related to the Kidney organ, characterized by symptoms such as weakness, coldness in the lower back and knees, feeling cold, fatigue, cold urine, frequent urination, nocturia, edema in the ankles, loose stools, infertility in women, impotence and decreased libido in men, premature ejaculation, low sperm count, pale and wet tongue, and weak pulse. There are several factors that can contribute to the development of kidney-Yang deficiency, such as chronic internal injuries (due to spleen-Yang deficiency or kidney-Yin deficiency), excessive sexual activity, overexertion, irregular diet, etc.¹ In the clinical treatment of kidney-Yang deficiency, traditional Vietnamese medicine utilizes a group of Yang tonifying herbs in various herbal formulas. Some valuable herbs used include Ba kích (Morinda officinalis), Nhục thung dung (Cistanche deserticola), Thỏ ty tử (Cuscuta chinensis), and so on.

The medicinal processing method is a unique technique in traditional medicine, both in general Eastern medicine and specifically in Vietnamese medicine. The medicinal processing method is based on theories (Yin and Yang, Five Elements, and Meridians) and folk experiences that enhance the therapeutic effects or create new therapeutic effects of medicines on the target organs. Additionally, some other purposes of processing medicinal materials may involve reducing or eliminating the adverse effects of drugs, thus avoiding discomfort for the patients.²

The processing procedures of traditional herbal medicines have been standardized and published by the Vietnamese Ministry of Health in Circular 30/2017/TT-BYT in 2017. Out of the 103 traditional herbal medicines listed in this document, five kidney-Yang tonifying herbs are processed using various procedures (as presented in Table 1).³

Table 1.

List of Processed Kidney-Yang Tonifying Herbs from Vietnamese Ministry of Health.³

No.	Name of ingredients	Plant name	Crude drug	Part used	Processing method
1	Ba kích	Morinda officinalis How.	Radix Morindae officinalis	Root	White wine-processed Salt-processed Licorice decoction-processed
2	Đỗ trọng	Eucommia ulmoides Oliv.	Cortex Eucommiae	Stem bark	White wine-processed Salt-processed Charcoal-processed
3	Nhục thung dung	Cistanche deserticola Y.C.Ma	Herba Cistanches	Stem	White wine-processed
4	Thỏ ty tử	Cuscuta chinensis Lam.	Semen Cuscutae	Seed	Salt-processed
5	Tục đoạn	Dipsacus asperoides C.Y.Cheng, et T.M.Ai./Dipsacus japonicus Miq.	Radix Dipsaci	Root	White wine-processed Salt-processed

This brief review aims to gather and assess the post-processing modifications to the chemical composition and the kidney-Yang tonifying effects of specific traditional herbal remedies. This intends to be a valuable resource for clinical practitioners of traditional medicine and provide scientific evidence for standardizing the preparation procedures.

Processing Procedures and Changes of Five Kidney-Yang Tonifying Herbs

Our review strategy is as follows: firstly, all kidney-Yang tonifying herbs categorized according to “The Foundations of Chinese Medicine: A comprehensive text, 3rd edition” were collected. Next, the selection was made based on the herbs with processing procedures specified in Circular 30/2017/TT-BYT issued by the Vietnamese Ministry of Health. All studies on the chemical composition and/or effects of processed drugs were searched in the PubMed and Google Scholar databases up to November 1, 2023, using the search formula: processed + scientific name of herbal medicine. Finally, among the studies on the changes in effects after processing, only studies on the Tonifying Yang effect were included in this review.

Five traditional herbs met the aforementioned selection criteria. From the PubMed and Google Scholar databases, 25 studies were collected for the review.

Radix Morindae officinalis—Vietnamese Name: Ba Kích

Processing

White Wine-Processed

A medicinal alcohol solution containing 30% to 40% alcohol (ratio 15% to herb ingredient, v/w) is mixed with Radix Morindae officinalis. The mixture is incubated for about 1 to 2 hours until the alcohol is fully absorbed and roasted with low heat until dry.³

Salt-Processed

A 5% saline solution (NaCl) (ratio 15% to herb ingredient, v/w) is mixed with Radix Morindae officinalis. The mixture is incubated for about 2 to 4 hours for being fully absorbed and roasted with low heat until dry.³

Licorice Decoction-Processed

Licorice (ratio 15% to herb ingredient, w/w) is decocted by boiling three times with water (at a 3-fold amount compared to the Licorice root) for 30 minutes each time and concentrating through evaporation to a specific volume (at a 15% ratio to the herbal material, v/w). The decoction is then mixed with Radix Morindae officinalis and the mixture is incubated for about 6 hours for being fully absorbed before being roasted with low heat until dry.³

Changes in Chemical Constituents

The phytochemical compounds of Radix Morindae officinalis have been extensively studied and reported to predominantly belong to various groups of compounds, including iridoid glycosides, anthraquinones, polysaccharides, organic acids, volatile oils, and more.⁴

Among the mentioned compound groups, the iridoid glycoside group exhibits many characteristic biological effects for Radix Morindae officinalis herbal medicine. One specific iridoid glycoside component in Radix Morindae officinalis was monotropein, which was determined to decrease in concentration by more than 30% after salt processing.⁵

A total of 55 chemical compounds between raw Radix Morindae officinalis and salt-processed Radix Morindae officinalis were found to undergo changes in their levels after analysis using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technique. Among these compounds, 29 belonged to the fructo-oligosaccharide group (including GF2 and GF21), 1,3-dihydroxy-2-methylanthraquinone-3-O-β-d-fructofuranose-(l→2)-β-d-fructofuranoside, monotropein, and deacetylasperulosidic acid. These compounds were found to have higher levels in raw Radix Morindae officinalis compared to salt-processed Radix Morindae officinalis. On the other hand, 26 compounds, including difructose anhydrides, iridoid glycoside derivatives, and sucrose, were found to have higher levels in salt processing herb.⁶

The content of polysaccharide compounds such as oligosaccharides GF7 (Fructo-oligosaccharide DP8) and GF8 (fructo-oligosaccharide DP9) decreased, while GF1 (sucrose) and GF2 (1-ketose) in Radix Morindae officinalis increased after processing (with salt and licorice decoction). Specifically, salt-processed Radix Morindae officinalis had a higher total oligosaccharide content compared to licorice decoction-processing one.⁷

Changes in Kidney-Yang Tonifying Activities

The pharmacological effects of Radix Morindae officinalis have been extensively studied and have been reported to have notable activities such as antioxidant, analgesic (pain-relieving), anti-inflammatory, anti-osteoporosis (bone-strengthening), and anxiolytic (reducing anxiety and depression) effects.³ According to traditional medicine, Radix Morindae officinalis is considered a Yang tonifying herb with a pungent and sweet taste, and warm nature, and it is associated with the Kidney meridian. In clinical practice, Radix Morindae officinalis is used for its functions of tonifying the kidney Yang, strengthening the tendons and bones, tonifying the Spleen and Stomach, benefiting essence, and more. It is commonly used to treat conditions such as kidney-Yang deficiency, spermatorrhea, impotence, knee weakness, and joint pain.⁸

Salt-processed Radix Morindae officinalis has been found to have better effects than licorice decoction-processing and raw ones in improving parameters such as body weight, testicular coefficient (the ratio of testicular weight to body weight), epididymal coefficient (the ratio of epididymal weight to body weight), serum testosterone, serum cortisol, and serum creatinine in adenine-induced kidney-Yang deficiency mice.⁹ Moreover, the energy exchange capacity in methimazole-induced kidney-Yang deficiency rats significantly increased when using salt-processed Radix Morindae officinalis compared to the group using the raw herb.¹⁰

Cortex Eucommiae—Vietnamese Name: Đỗ Trọng

Processing

Salt-Processed

A saline solution (NaCl) (ratio 17% to herb ingredient, v/w, prepared by dissolving 0.03 g of salt in 170 mL of distilled water) is mixed with Cortex Eucommiae. The mixture is incubated for about 1 hour for being fully absorbed and roasted with medium heat until the threads break.³

White Wine-Processed

A medicinal alcohol solution (ratio 20% to herb ingredient, v/w) is mixed with Cortex Eucommiae. The mixture is incubated for about 1 hour for being fully absorbed and roasted with medium heat until the threads break.³

Charcoal-Processed

Cortex Eucommiae is roasted with a strong heat, stirring continuously until white smoke appears and all the threads break. A small amount of distilled water is sprayed and the material is roasted with a small heat for about 2 to 3 minutes before removing and cooling.³

Changes in Chemical Constituents

More than 200 phytochemical compounds have been extracted, isolated, and successfully identified in Cortex Eucommiae, belonging to various groups such as lignans, iridoids, flavonoids, phenolic acids, sterols, fatty acids, volatile oils, and more. Among these, lignans are a group of compounds that exhibit numerous valuable biological effects of Cortex Eucommiae.¹¹

The number of compounds as well as the content of pinoresinol diglucoside in salt processing Cortex Eucommiae was lower compared to raw herbal medicine when analyzed by high-performance liquid chromatography (HPLC). The evaluated chemical compounds included pinoresinol diglucoside, genipin, geniposide, geniposidic acid, caffeic acid, chlorogenic acid, and quercetin, which showed a dramatical decrease in content after processing (salt processing and charcoal processing), as demonstrated in Table 2.¹²

Table 2.

The Changes in the Content of Several Compounds in Salt Processing and Charcoal Processing Cortex Eucommiae.¹²

Chemical compound	Decrease in content (compared to raw form)
Chemical compound	Salt-processed	Charcoal-processed
Pinoresinol diglucoside	30%	85%
Genipin	25%	98%
Geniposide	40%	70%
Geniposidic acid	40%	70%
Caffeic acid	75%	75%
Chlorogenic acid	40%	75%
Quercetin	60%	50%

The charcoal-frying process of Cortex Eucommiae was proven to degrade several chemical compounds, such as geniposidic acid, chlorogenic acid, genipin, licoagrosid F, and syringaresinol di-O-β-d-glucopyranoside. The compounds wogonin and oroxylin A were completely degraded after charcoal frying, while three other compounds, geniposide, pinoresinol-di-O-β-d-glucopyranoside, and baicalein, had an increase after the processing. On the other hand, the salt-processed process increased the extractability of chlorogenic acid in Cortex Eucommiae without statistically degrading other compounds.¹³

Changes in Kidney-Yang Tonifying Activities

Studies on the pharmacological effects of Cortex Eucommiae have provided scientific evidence of its medicinal effects, including blood pressure-lowering, blood sugar-lowering, antibacterial, anti-inflammatory, immune-modulating, anti-tumor, antioxidant, and anti-osteoporosis effects.¹¹ According to traditional medicine, Cortex Eucommiae is described as having a sweet and spicy taste, and warm properties, and acts to the Kidney and Liver organs. It is believed to tonify the Kidney, strengthen the tendons and bones, support pregnancy, and regulate blood pressure. Moreover, Cortex Eucommiae is used clinically to treat conditions such as liver–kidney deficiency, lower back pain, knee weakness, joint pain, spermatorrhea, impotence, and more.⁸

Raw Cortex Eucommiae was proven to have a regulatory effect on the secretion of corticosterone in the adrenal cortex and tri-iodothyronine, and tetra-iodothyronine in the hypothalamus–pituitary–thyroid axis in kidney-Yang deficiency mice. On the other hand, salt-processed herbal medicine showed improvements in these parameters in the treating group.¹⁴

Herba Cistanches—Vietnamese Name: Nhục Thung Dung

Processing

An alcohol solution (ratio 30% to herb ingredient, v/w) is mixed with Herba Cistanches. The mixture is steamed for about 24 to 48 hours until black or golden brown in color.³

Changes in Chemical Constituents

Chemical composition analysis papers of Herba Cistanches have demonstrated the presence of over 100 compounds. Common groups of compounds found in Herba Cistanches include essential oils, iridoids, lignans, alditols, polysaccharides, phenylethanoid glycosides, and more.¹⁵

The total content of phenylethanoid glycosides, polysaccharides, isoacteoside, and osmanthuside B in wine-processed Herba Cistanches was significantly higher compared to raw herbal medicine. Additionally, the content of phenylethanoid glycosides with a 6′-O-caffeoyl group attached to the 8-O-β-d-glucopyranosyl moiety, such as isoacteoside, isocistanoside C, isocampneoside I, and isomartynoside, was also numerous higher in the processed one. However, the content of 2′-acetylacteoside, acteoside, and phenylethanoid glycosides with a 4′-O-caffeoyl group attached to the 8-O-β-d-glucopyranosyl moiety (acteoside, cistanoside C, campneoside II, osmanthuside) decreased substantially after processing with wine.^16,17

The results of the ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) analysis combined with proposed molecular networking data identified 34 chemical compounds that can be used to differentiate raw and wine-processed Herba Cistanches (marker compounds). Among these compounds, 6 belong to the iridoid group (kankanoside B, mussaenosid acid, 8-epiloganic acid, adoxosidic acid, kankanoside A, and kankanoside N), 20 belong to the phenylethanoid glycoside group (kankanoside F, decaffeoylacteoside, cistantubuloside C1/2, cistanoside H, campneoside II, decaffeoylacteoside, acteoside, crenatoside, isocampneoside I, brandioside, isosyringalid A 3′-α-l-rhamnopyranoside, kankanoside J1, pheliposide, kankanoside G, isocistanoside C, osmanthuside B, cistubuloside B, and tubuloside E), and 12 are other compounds (kankanose, cistanoside F, (2E,6Z)-8-β-d-glucopyranosyloxy-2,6-dimethyl-2,6-octadienoic acid, kankanoside O, (+)-pinoresinol-O-β-d-glucopyranoside, (+)-syringaresinol-O-β-d-glucopyranoside, salsaside B, and dibutyl sebacate).¹⁸

In 2023, Hou et al conducted a study on the changes in polysaccharide composition among different forms of Herba Cistanches, including raw samples, enzymatic hydrolysis, hot air drying, wine processing, and high-pressure steaming. The results revealed that the polysaccharide component of the wine-processing Herba Cistanches exhibited compact structures and had the largest molecular chain compared to the polysaccharide components in the other forms of herbal medicine.¹⁹

Changes in Kidney-Yang Tonifying Activities

Research on the biological activities of Herba Cistanches has been conducted and reported with pharmacological effects such as improving brain function, enhancing libido, and boosting the immune system.¹⁵ According to traditional medicine, Herba Cistanches is believed to have functions in tonifying the Kidney, strengthening Yang, and promoting bowel movements, and is used in treating syndromes related to kidney-Yang deficiency or constipation.⁸

Kidney-Yang deficiency male mice treated with raw Herba Cistanches showed restoration of the levels of sex hormones (testosterone and estradiol), improvement in antioxidant effects, and increased kidney, seminal vesicle, epididymis, and testicular weights. Specifically, the group of mice treated with wine-processed Herba Cistanches exhibited typically better increases in kidney and seminal vesicle weights compared to unprocessed ones.¹⁹

In 2020, Liu et al conducted a study comparing the immune-endocrine function of different forms of Herba Cistanche in kidney-Yang deficiency rats induced by glucocorticoids. The results showed that the groups of rats treated with both raw and processed Herba Cistanche exhibited increased weights of the adrenal glands and spleen. They also showed dramatic changes in the levels of serum hormones such as testosterone, CRH, ACTH, CORT, and cortisol. The immune factors IL-4 and IL-8, the CD4+/CD8+ ratio, and the expression of Bcl-2, caspase-3, Fas, FasL, and CaM in the pseudo-synovial tissue were also significantly different compared to the control group. Additionally, the concentrations of IL-6, TNF-α, IFN-γ, and the expression of CaM mRNA in the hypothalamic–pituitary region decreased in the experimental groups.²⁰

Semen Cuscutae—Vietnamese Name: Thỏ ty tử

Processing

A saline solution (ratio 15% to herb ingredient, v/w, prepared by dissolving 20 g of salt in 150 mL of distilled water) is mixed with Semen Cuscutae. The mixture is incubated for about 30 minutes for being fully absorbed and roasted with low heat until the particles start to expand, and the mixture turns a golden brown color with a mild and pleasant aroma.³

Changes in Chemical Constituents

The reports on the phytochemical composition of Semen Cuscutae indicate the presence of various chemical compounds belonging to different groups such as flavonoids, polysaccharides, alkaloids, steroids, volatile oils, lignans, and more. These compounds are believed to contribute to the therapeutic effects of the herbal medicine.²¹ Figure 1 illustrates the chemical structures of some compounds in Semen Cuscutae that were affected by the processing procedures.

Figure 1.

The chemical formulas of the five compounds in Semen Cuscutae influenced by the processing method.

The HPLC analysis results showed that Semen Cuscutae can be differentiated between the raw form and the salt processing form based on five compounds: hyperoside, astragalin, kaempferol, isorhamnetin, and quercetin. The content of hyperoside was found to decrease in the salt-processed Semen Cuscutae, while the other four compounds (astragalin, kaempferol, isorhamnetin, and quercetin) were found to have higher levels in the processed form compared to the raw one. Furthermore, the total flavonoid content in the salt-roasted Semen Cuscutae extract showed a statistically significant increase compared to the raw herb.²²

Another published study reported a statistically significant increase in the content of certain chemical compounds (3-caffeoylquinic acid, 4-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, caffeic acid, 5-O-feruloylquinic acid, p-hydroxycinnamic acid, astragalin, kaempferol, isorhamnetin, isoquercitrin, and luteolin-7-O-glucoside) in Semen Cuscutae after salt and wine processing. The analysis results revealed that two compounds, hyperoside, and 3-caffeoylquinic acid, had high levels in the processed Semen Cuscutae samples.²³

In addition, Changli et al demonstrated that the processing temperature was a factor that led to changes in the content of six phytochemical compounds (neoclorogenic acid, cryptophyllogenic acid, caffeic acid, quercetin, isorhamnetin, and kaempferol) between raw and processed Semen Cuscutae.²⁴

Changes in Kidney-Yang Tonifying Activities

Semen Cuscutae has been extensively studied and shown to possess numerous pharmacological effects such as skin protection, liver protection, anti-osteoporosis properties, immune-modulating effects, antioxidant activity, anti-aging effects, effects on the reproductive system, and kidney protection.²¹ In traditional medicine, Semen Cuscutae is used for its tonifying and strengthening properties on the kidney Yang, brightening eyes, and benefiting urinary function. It is commonly utilized in the treatment of diseases related to kidney-Yang deficiency, liver–kidney weakness, frequent urination, and blood in the urine.⁸

Hydrocortisone sodium succinate-induced kidney-Yang deficiency rats treated with raw Semen Cuscutae increased in the weight of the kidney, testes, epididymis, and prostate. On the other hand, treatment with salt-processed Semen Cuscutae led to an increase in the weight of the kidney, testes, epididymis, and seminal vesicles. Furthermore, both raw and processed herbal medicine treatments showed positive signs in immune function, including the regulation of T-cell subgroups and a decrease in the concentration of IgG and IgM in the blood.²²

Radix Dipsaci—Vietnamese Name: Tục Đoạn

Processing

Salt-Processed

A saline solution (ratio 2% to herb ingredient, v/w) is mixed with Radix Dipsaci. The mixture is incubated for being fully absorbed and roasted with small heat until dry.³

White Wine-Processed

A medicinal alcohol solution (ratio 15%-20% to herb ingredient, v/w) is mixed with Radix Dipsaci. The mixture is incubated for being fully absorbed and roasted with small heat until dry.³

Changes in Chemical Constituents

The studies on the chemical composition of Radix Dipsaci indicated that phytochemical properties belonging to the group of oleanane-type triterpenoids are the main components responsible for its biological effects. Additionally, various compounds from different groups such as iridoids, phenolics, essential oils, alkaloids, lignans, fatty acids, and others have been isolated and identified through research. These findings highlight the diverse array of chemical constituents present in Radix Dipsaci, which contribute to its therapeutic properties.²⁵

In 2014, Song et al conducted a study on the variation of asperosaponin VI, a signature compound of Radix Dipsaci, through alcohol frying using HPLC analysis. Three factors of the processing procedure of Radix Dipsaci were investigated using an orthogonal design at four levels: alcohol-to-herb ratio (10, 15, 20, and 25%), frying time (6, 8, 10, and 12 minutes), and frying temperature (100, 130, 160, and 190 °C). The results revealed that the frying temperature had a significant impact on the variation of asperosaponin VI content in Radix Dipsaci, and an optimized processing procedure was proposed, which included an alcohol-to-herb ratio of 15%, a frying time of 6 minutes, and a frying temperature of 100 °C.²⁶

In 2015, Luo et al reported the differences in chemical composition between raw Radix Dipsaci and Radix Dipsaci processed with alcohol using HPLC analysis. The results indicated that the processing with alcohol increased the content of asperosaponin VI in Radix Dipsaci and revealed the appearance of two new peaks in the chromatographic fingerprint region. This suggested that the processing method with alcohol-induced changes in the chemical profile of Radix Dipsaci led to the alteration and emergence of additional compounds in its chromatographic pattern.²⁷

In 2016, using the advanced analytical technique UPLC-Q-TOF/MS, Tao et al observed a greater variation in the content of various plant phytochemicals in Radix Dipsaci processed with alcohol. The analysis results revealed an increase in the content of compounds such as asperosaponin VI, acetylated derivatives, and caffeic acid analogs in the alcohol-processed Radix Dipsaci. However, the content of phenolic compounds, such as dicaffeoylquinic acid, was lower in the alcohol-processed herbal medicine.²⁸

In 2018, Tao et al continued their research by developing a simultaneous quantification method for eight chemical compounds in Radix Dipsaci using UHPLC–MS/MS. They applied this method to compare the chemical composition between raw Radix Dipsaci and Radix Dipsaci processed with alcohol. The quantification results showed that four out of the eight chemical compounds increased in content after processing, including loganic acid, chlorogenic acid, dipsacoside B, and asperosaponin VI. On the other hand, the levels of four compounds, namely 3,5-dicaffeoylquinic acid, 4-caffeoylquinic acid, loganin, and sweroside, were lower in the alcohol-processed Radix Dipsaci.²⁹

In 2019, Tao et al upgraded and improved the quantification process of phytochemical compounds in Radix Dipsaci using UPLC-Q-TOF/MS. The quantification method aimed to determine the levels of 10 compounds, including loganic acid, loganin, 3,5-dicaffeoylquinic acid, 4-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, sweroside, dipsacussaponin B, dipsacoside A, asperosaponin V, and asperosaponin VI, and applied it to quantify these compounds in alcohol-processed Radix Dipsaci. The results showed that five compounds, namely loganic acid, asperosaponin VI, dipsacus saponin B, dipsacoside A, and asperosaponin V, increased in content after processing. Conversely, the remaining five chemical compounds exhibited a decrease in content in the alcohol-processed herbal medicine.³⁰

Changes in Kidney-Yang Tonifying Activities

Radix Dipsaci is a medicinal herb that has been extensively studied in traditional medicine for its various pharmacological effects. It has been shown to have benefits such as anti-osteoporosis, bone fracture healing, neuroprotective properties, uterine relaxation, anti-aging effects, liver protection, anti-myocardial ischemia, anti-inflammatory properties, and anti-rheumatic effects.²⁵ According to the theories of traditional medicine, Radix Dipsaci is considered a Yang tonifying herb with actions that tonify the Kidney, strengthen the tendons and bones, promote Blood circulation, regulate the meridians, detoxify the body, and treat acne.⁸

Regarding the therapeutic effects on kidney-Yang deficiency, rats treated with alcohol-processed Radix Dipsaci showed improved organ parameters, hormone levels, and activity of certain enzymes, which were statistically significant compared to raw Radix Dipsaci.³¹

Discussion

In the clinical practice of traditional medicine, tonic remedies containing Yang tonifying herbs are commonly used to treat kidney-Yang deficiency. Processing methods such as roasting or salt-processed are employed to enhance the Yang nature and reduce the Yin nature of the herbs.¹ Some herbs are processed into charred form (Cortex Eucommiae) or salt-processed form (Radix Morindae officinalis, Cortex Eucommiae, Semen Cuscutae, and Radix Dipsaci) to direct the herbs’ effects toward the Kidney meridian, according to the theories of Five Elements and Meridians. Additionally, three herbs, namely Cortex Eucommiae, Herba Cistanches, and Radix Dipsaci, can also be processed with white wine (alcohol) to increase their warm and ascending properties, thereby enhancing the Yang nature of the herbal medicine.¹ Currently, there have been numerous modern pharmacological studies published to provide support for the theories of herbal processing in traditional medicine, as presented in Table 3.

Table 3.

Summary of the Influence of Processing on Kidney-Yang Tonifying Herbal Medicines.

	Name of herbal medicine	The influence of processing
	Name of herbal medicine	Chemical constituents	Kidney-Yang tonifying effect
1	Ba kích (Radix Morindae officinalis)	↓ content: monotropein⁵, fructo-oligosaccharide DP8, fructo-oligosaccharide DP9 ⁶ ↑ content: sucrose, 1-ketose, difructose anhydride, and iridoid glycoside derivatives^6,7	Improvement: body weight, testicular coefficient, epididymal coefficient, serum testosterone, serum cortisol, serum creatinine, level of liver glycogen, muscule glycogen, free fatty acid, lipoprotein lipase, liver lipase, Na⁺–K⁺-ATPase, Ca²⁺–Mg²⁺-ATPase, SDH^9,10 Chemical compounds related to the Kidney-Yang tonifying effect: monotropein, deacetyl asperulosidic acid, asperulosidic acid, and asperuloside³²
2	Đỗ trọng (Cortex Eucommiae)	↓ content: pinoresinol diglucoside, genipin, geniposide, geniposidic acid, caffeic acid, chlorogenic acid, and quercetin¹² ↑ content: geniposide, pinoresinol-di-O-β-d-glucopyranoside, and baicalein¹³ Decomposition: wogonin and oroxylin A¹³	Improvement: regulatory effect on the secretion of corticosterone in the adrenal cortex and tri-iodothyronine, tetra-iodothyronine in the hypothalamus–pituitary–thyroid axis¹⁴ Chemical compounds related to the Kidney-Yang tonifying effect: geniposidic acid, chlorogenic acid, geniposide, genipin, pinoresinol diglucoside, and hyperoside³³ Kidney-Yang tonifying targeted proteins: AKT1 and PTGS2¹⁴
3	Nhục thung dung (Herba Cistanches)	↓ content: 2′-acetylacteoside, acteoside, phenylethanoid glycosides with a 4′-O-caffeoyl group attached to the 8-O-β-d-glucopyranosyl moiety^16,17 ↑ content: phenylethanoid glycoside, polysaccharide, isoacteoside, osmanthusid B, phenylethanoid glycosides with a 6′’-O-caffeoyl group attached to the 8-O-β-d-glucopyranosyl moiety ^16,17	↑: kidney, seminal vesicle, epididymis, testicular weights, adrenal glands, spleen, testosterone, CRH, ACTH, CORT, and cortisol. The immune factors IL-4 and IL-8, the CD4+/CD8+ ratio, and the expression of Bcl-2, caspase-3, Fas, FasL, and CaM in the pseudo-synovial tissue^19,20 ↓: IL-6, TNF-α, IFN-γ, and the expression of CaM mRNA in the hypothalamic–pituitary region²⁰ Kidney-Yang deficiency treatment mechanism: counteracting dysregulated reproductive hormones and immune factors in mice subjected to excessive glucocorticoid dosing; observing enhancing and restoring effects on the hypothalamic–pituitary–adrenal axis and improving immune function²⁰
4	Thỏ ty tử (Semen Cuscutae)	↓ content: hyperoside²² ↑ content: hyperin, quercetin, kaempferol, total flavonoid, 3-caffeoylquinic acid, 4-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, caffeic acid, 5-O-feruloylquinic acid, p-hydroxycinnamic acid, astragalin, kaempferol, isorhamnetin, isoquercitrin, and luteolin-7-O-glucoside²³	↑: weight of the kidney, testes, epididymis, and prostate (raw); weight of the kidney, testes, epididymis, and seminal vesicles (processed)²² Regulation of T-cell subgroups and a decrease in the concentration of IgG and IgM in the blood²²
5	Tục đoạn (Radix Dipsaci)	↓ content: dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 4-caffeoylquinic acid, loganin, swerosid, and 3,4-dicaffeoylquinic acid^27–30 ↑ content: asperosaponin VI, acetylated derivatives and caffeic acid, loganic acid, chlorogenic acid, dipsacoside B, dipsacoside A, and asperosaponin V^27–30 Optimized processing procedure: alcohol-to-herb ratio of 15%, frying time of 6 minutes, and frying temperature of 100°C²⁶	↑: organ parameters, hormone levels, (ACTH, CORT, T4, TNF-α, testosterone, estradiol, and GH), and activity of certain enzymes (cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), Na⁺–K⁺-ATPase); expression of proteins Smad 1, Smad 4, Smad 5, Smad 8, and BMP 7 in kidney³¹ Kidney-Yang deficiency treatment mechanism: intervention in the BMP-Smad signaling pathway³¹

The correlation between the chemical components and the Yang tonifying effects of salt-processed Radix Morindae officinalis has been determined using modern analytical techniques such as UPLC-DAD combined with multivariate statistical analysis. Thirteen compounds that are correlated with the functional properties of salt-processed Radix Morindae officinalis according to traditional medicine have been identified, including four compounds: monotropein, deacetyl asperulosidic acid, asperulosidic acid, and asperuloside (as presented in Figure 2).³²

Figure 2.

Chemical formulas of the compounds with Yang tonifying effects in Radix Morindae officinalis.

Monotropein, a major iridoid compound in Radix Morindae officinalis, possessed various biological effects, with its most prominent being its anti-osteoporotic activity.³⁴ According to traditional medicine, the Kidney controls bones. When the Kidney essence is abundant, the bone marrow is full, and the limbs move gently, gracefully, and stand firmly.¹ Therefore, the anti-osteoporotic effect of monotropein may be related to its kidney-Yang tonifying properties in Radix Morindae officinalis. Additionally, several other compounds in Radix Morindae officinalis have been demonstrated to be associated with kidney Yang-nourishing effects, including deacetyl asperulosidic acid, asperulosidic acid, and asperuloside (as presented in Figure 2).³² Although the processing of Radix Morindae officinalis reduced the content of monotropein and deacetyl asperulosidic acid, it increased the levels of two other iridoid glycosides, asperulosidic acid, and asperuloside.^5,6 Additionally, the salt processing of Radix Morindae officinalis has been demonstrated to enhance the absorption and bioavailability of monotropein,³⁵ contributing to the increased Yang-tonifying effects of the herbal medicine. However, the mechanisms underlying the transformation of compounds in Radix Morindae officinalis need to be further investigated.

Cortex Eucommiae is also a commonly used Yang-tonifying herb in clinical practice. In addition to sensory characteristics such as color and taste, the two forms of Cortex Eucommiae, raw and salt-processed, can be differentiated through the analysis of 11 marker compounds. These compounds included geniposidic acid, neochlorogenic acid, chlorogenic acid, caffeic acid, geniposide, genipin, pinoresinol di-O-glucopyranoside, syringaresinol di-O-glucopyranoside, isochlorogenic acid A, pinoresinol O-glucopyranoside, and isochlorogenic acid. Among these 11 marker compounds, six phytochemical compounds have been demonstrated to be associated with the Yang tonifying effects of Cortex Eucommiae, namely geniposidic acid, chlorogenic acid, geniposide, genipin, pinoresinol diglucoside, and hyperoside (as presented in Figure 3).³³ The target proteins involved in the Yang tonifying effects of these six chemical compounds have been identified through molecular docking and pharmacological network analysis as AKT1 and PTGS2.¹⁴

Figure 3.

Chemical formulas of the compounds with Yang tonifying effects in Cortex eucommiae.

Geniposide, found in Cortex Eucommiae, has been shown to have various pharmacological effects such as inhibiting cognitive decline (Alzheimer's), reducing local ischemia, alleviating depression, and modulating the immune system.³⁶ According to traditional medicine theory, the Kidney is the “residence” of Will power. When the Kidney is weakened, the willpower also weakens, leading to weakness, lack of effort and initiative, easily becoming disheartened, and being prone to giving up on set goals. Lack of willpower and motivation are often key factors in depression, and Kidney tonification generally yields positive results. In elderly individuals, Kidney deficiency can also manifest as decreased memory, and in more severe cases, confusion.¹ Therefore, geniposide can be regarded as a marker compound with Kidney-Tonifying effects in herbal medicine. The process of charred Cortex Eucommiae is also theoretically believed to enhance the effects of the herb on the Kidney meridian according to traditional medicine. This theory is supported by reports demonstrating an increase in the levels of geniposide in charcoal-processed Cortex Eucommiae.¹³ However, there was conflicting data regarding the content of geniposide in charcoal-processed Cortex Eucommiae between the reports of Tao and Chai, and there was no explanation regarding the mechanisms of compound transformation. This difference may be influenced by processing conditions such as processing temperature, processing time, and frequency of material stirring. Furthermore, the content of compounds in Charcoal-processed Cortex Eucommiae was only determined in 1 or 2 batches of processed herbal materials, which may not be representative of the overall processed Cortex Eucommiae. Further research is needed to conduct comprehensive evaluations and provide more conclusive findings.

The processing of Herba Cistanches is believed to involve the transformation of phenylethanoid glycosides through two reactions: hydrolysis and esterification. In an ethanol environment, the functional groups on phenylethanoid glycosides are replaced by hydroxyl groups (-OH). Subsequently, the 4′-O-caffeoyl group was cleaved from the structure, forming caffeic acid, which reduced the content of phenylethanoid glycosides with 4′-O-caffeoyl at the 8-O-β-d-glucopyranosyl position. The formed caffeic acid then participated in esterification reactions at the 6′-OH position, increasing the content of phenylethanoid glycosides with 6′-O-caffeoyl at the 8-O-β-d-glucopyranosyl position. Additionally, Li et al suggested the occurrence of a rearrangement reaction of the caffeoyl group at the 4′-6′ position of phenylethanoid glycosides during the processing of Herba Cistanches. Figure 4 depicts the degradation process of cistanoside C, a phenylethanoid glycoside compound, during the processing of Herba Cistanches.^16,17

Figure 4.

The transformation process of active compounds in Herba Cistanches after processing (eg cistanoside C).

The Yang tonifying effects of raw/processed Herba Cistanches have been demonstrated by Liu et al Based on their research findings, the authors suggested that different forms of Herba Cistanches were able to counteract dysregulated reproductive hormones and immune factors in mice subjected to excessive glucocorticoid dosing. They also observed enhancing and restoring effects on the hypothalamic–pituitary–adrenal axis and improving immune function.²⁰

In addition to improving organ parameters, hormones, and enzyme activities after treatment with different forms of Radix Dipsaci, the expression of proteins Smad 1, Smad 4, Smad 5, Smad 8, and BMP 7 in the kidneys of treated batches also significantly increased. Specifically, signals observed in the group treated with salt-processed Radix Dipsaci were more significant compared to the raw form. Based on these findings, the authors proposed that the mechanism of action for treating kidney-Yang deficiency with salt-processed Radix Dipsaci involved intervention in the BMP-Smad signaling pathway.³¹

Conclusion

The kidney Yang-nourishing effects of the five traditional herbal medicines prescribed in Circular 30/2017/TT-BYT by the Ministry of Health of Vietnam (Radix Morindae officinalis, Cortex Eucommiae, Herba Cistanches, Semen Cuscutae, and Radix Dipsaci) have been demonstrated through several studies and summarized in our review. Additionally, the changes in composition and content of certain active compounds in these herbal medicines have also been searched and reported. However, the evidence regarding the mechanisms of chemical compound transformation in these herbal medicines, as well as the relationship between chemical composition and kidney-Yang tonifying effects, is still limited. Therefore, further research in this field is needed to gain a deeper understanding.

Footnotes

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Minh-Nhut Truong

Lan-Phuong Le Thi

References

Maciocia

. The foundations of Chinese medicine: a comprehensive text, vol. 162. 3rd ed. Churchill Livingstone; 2015:451-467.

Sionneau

. Pao Zhi: an introduction to the use of processed Chinese medicinals. Blue Poppy Enterprises, Inc.; 1995.

Ministry of Health. Circular 30/2017/TT-BYT on “Directions guide to processing methods of traditional ingredients”. Hanoi, July 11^th, 2017.

Zhang

Xin

, et al. Morinda officinalis how. - A comprehensive review of traditional uses, phytochemistry and pharmacology. J Ethnopharmacol. 2018;213:230-255. doi:https://doi.org/10.1016/j.jep.2017.10.028

Liang

Ding

. Determination of monotropein in Radix Morindae from different processed products by HPLC. Zhong yao cai. 2007;30(1):20-22.

Kang

Zhang

Zhou

, et al. Structural characterization and discrimination of Morinda officinalis and processing Morinda officinalis based on metabolite profiling analysis. Front Chem. 2021;9:803550. doi:https://doi.org/10.3389/fchem.2021.803550

Zhou

Zhang

, et al. Calculating relative correction factors for quantitative analysis with HILIC-HPLC-ELSD method: eight fructooligosaccharides of Morinda Officinalis as a case study. J Anal Methods Chem. 2022;2022:8022473. doi:https://doi.org/10.1155/2022/8022473

Zhang-fu

De-xian

Bare

. Chinese Materia Medica. People’s Medical Publishing House. 2014:571,573,578,579,586,587.

Cui

Shi

Jia

. Comparative study on kidney tonifying and yang supporting effects of different processed products of Morinda officinalis. Zhongguo Zhong yao za zhi. 2013;38(22):3898-3901.

10.

Huang

Fan

Jia

, et al. Effect of Morinda officinalis root and its salt-processing product on energy metabolism in rats with yang deficiency. Zhong yao cai. 2016;39(5):1028-1031.

11.

Wang

Tang

, et al. Ethnobotany, phytochemistry and pharmacological properties of Eucommia ulmoides: a review. Am J Chin Med. 2019;47(2):259-300. doi:https://doi.org/10.1142/s0192415(19500137

12.

Tao

Sheng

, et al. Investigation on chemical constituents of processed products of Cortex Eucommiae. Zhongguo Zhong yao za zhi. 2014;39(22):4352-4355.

13.

Chai

Wang

, et al. A rapid ultra performance liquid chromatography-tandem mass spectrometric method for the qualitative and quantitative analysis of ten compounds in Eucommia ulmodies Oliv. J Pharm Biomed Anal. 2012;57:52-61. doi: https://doi.org/10.1016/j.jpba.2011.08.023

14.

Zhuang

Lin

, et al. Enrichment of the flavonoid fraction from Eucommia ulmoides leaves by a liquid antisolvent precipitation method and evaluation of antioxidant activities in vitro and in vivo. RSC Adv. 2023;13(25):17406-17419. doi:https://doi.org/10.1039/d3ra00800b

15.

Lin

, et al. Herba Cistanche (Rou Cong-Rong): one of the best pharmaceutical gifts of traditional Chinese medicine. Front Pharmacol. 2016;7:41. doi: https://doi.org/10.3389/fphar.2016.00041

16.

Zhang

Wang

Yang

, et al. The difference of chemical components and biological activities of the raw products slices and the wine steam-processed product from Cistanche deserticola. Evid Based Complement Alternat Med. 2019;2019:2167947. doi: https://doi.org/10.1155/2019/2167947

17.

Ryenchindorj

Liu

, et al. Chemical profiles and metabolite study of raw and processed Cistanche deserticola in rats by UPLC-Q-TOF-MSE. Chin Med. 2021;16(1):95. doi: https://doi.org/10.1186/s13020-021-00508-0

18.

Lei

Zhang

, et al. Comprehensive profiling of the chemical components and potential markers in raw and processed Cistanche tubulosa by combining ultra-high-performance liquid chromatography coupled with tandem mass spectrometry and MS/MS-based molecular networking. Anal Bioanal Chem. 2021;413(1):129-139. doi: https://doi.org/10.1007/s00216-020-02983-0

19.

Hou

Tan

Chang

, et al. Effects of different processing (Paozhi) on structural characterization and antioxidant activities of polysaccharides from Cistanche deserticola. Int J Biol Macromol. 2023;245:125507. doi: https://doi.org/10.1016/j.ijbiomac.2023.125507

20.

Liu

Shi

, et al. Study on neuroendocrine-immune function of Cistanche deserticola and its rice wine steaming products in glucocorticoid-induced rat model. Evid Based Complement Alternat Med. 2020;2020:5321976. doi: https://doi.org/10.1155/2020/5321976

21.

Donnapee

Yang

, et al. Cuscuta chinensis Lam.: a systematic review on ethnopharmacology, phytochemistry and pharmacology of an important traditional herbal medicine. J Ethnopharmacol. 2014;157:292-308. doi:https://doi.org/10.1016/j.jep.2014.09.032

22.

Yang

Zhao

, et al. The difference of chemical components and biological activities of the crude products and the salt-processed product from Semen Cuscutae. Evid Based Complementary Altern Med. 2016;2016:8656740. doi:https://doi.org/10.1155/2016/8656740

23.

Zhang

Liu

, et al. Comparative studies on chemical contents and effect in kidney-Yang deficiency rats of salt-processed product and wine-processed product of Cuscutae Semen. Evid Based Complementary Altern Med. 2019;2019:2049497. doi:https://doi.org/10.1155/2019/2049497

24.

Changli

Yun

Hua

, et al. Comparative investigation between raw and stir-frying processed Cuscutae Semen based on HPLC fingerprints coupled with chemometric methods. J AOAC Int. 2023;106(4):1037-1047. doi: https://doi.org/10.1093/jaoacint/qsad002

25.

Tao

Chen

Yan

. Traditional uses, processing methods, phytochemistry, pharmacology and quality control of Dipsacus asper Wall. ex C.B. Clarke: a review. J Ethnopharmacol. 2020;258:112912. doi:https://doi.org/10.1016/j.jep.2020.112912

26.

Song

Wang

Duan

, et al. Chromatographic fingerprint combined with content of asperosaponin VI and antioxidant activity for quality evaluation of wine-fried Dipsaci Radix. Nat Prod Commun. 2014;9(6):773-778.

27.

Luo

Qing

Zhang

, et al. HPLC fingerprint and analysis of component difference of crude and wine processed products for Dipsacus asper root. Zhong Yao Cai. 2015;38(3):493-496.

28.

Tao

Jiang

Tang

, et al. Comparisons on chemical constituents of crude and wine-processed Dipsacus asper by using UPLC-Q-TOF/MS. Zhongguo Zhong Yao Za Zhi. 2016;41(4):672-676. doi: https://doi.org/10.4268/cjcmm20160421

29.

Tao

, et al. UHPLC–MS/MS quantification combined with chemometrics for the comparative analysis of different batches of raw and wine-processed Dipsacus asper. J Sep Sci. 2017;40(8):1686-1693. doi: https://doi.org/10.1002/jssc.201601459

30.

Tao

Huang

, et al. Simultaneous determination of ten bioactive components in raw and processed Radix Dipsaci by UPLC-Q-TOF-MS. J Chromatogr Sci. 2019;57(2):122-129. doi: https://doi.org/10.1093/chromsci/bmy093

31.

, et al. Research on the effect of Dipsaci Radix before and after salt-processed on kidney yang deficiency syndrome rats and the preliminary mechanism study through the BMP-Smad signaling pathway. J Ethnopharmacol. 2023;312:116480. https://doi.org/10.1016/j.jep.2023.116480

32.

Zhang

Fan

Yang

, et al. Discovering the main “reinforce kidney to strengthening Yang” active components of salt Morinda officinalis based on the spectrum-effect relationship combined with chemometric methods. J Pharm Biomed Anal. 2022;207:114422. https://doi.org/10.1016/j.jpba.2021.114422

33.

Guo

Tang

Wei

Xiao

Yang

. Possible pharmaceutical effect and active components in different parts of Eucommia ulmoides based on network pharmacology. Zhongguo Zhong yao za zhi. 2020;45(8):1800–1807. https://doi.org/10.19540/j.cnki.cjcmm.20200107.401

34.

Lai

Peng

, et al. Monotropein: A comprehensive review of biosynthesis, physicochemical properties, pharmacokinetics, and pharmacology. Front Pharmacol. 2023;14:C572. https://doi.org/10.3389/fphar.2023.1109940

35.

Shi

Ren

Wang

Wei

Liu

Jia

. Effects of the Salt-Processing Method on the Pharmacokinetics and Tissue Distribution of Orally Administered Morinda officinalis How. Extract. J Anal Methods Chem. 2020;2020:1–11. https://doi.org/10.1155/2020/5754183

36.

Zhou

Zhang

Rahman

Cao

Zhang

Peng

. Diverse Pharmacological Activities and Potential Medicinal Benefits of Geniposide. Evid Based Complement Alternat Med. 2019;2019:1–15. https://doi.org/10.1155/2019/4925682

Changes in Chemical Constituents and Kidney-Yang Tonifying of Traditional Herbs After Processing: A Brief Review

Abstract

Background

Methodology

Results

Conclusion

Keywords

Introduction

Processing Procedures and Changes of Five Kidney-Yang Tonifying Herbs

Radix Morindae officinalis—Vietnamese Name: Ba Kích

Processing

White Wine-Processed

Salt-Processed

Licorice Decoction-Processed

Changes in Chemical Constituents

Changes in Kidney-Yang Tonifying Activities

Cortex Eucommiae—Vietnamese Name: Đỗ Trọng

Processing

Salt-Processed

White Wine-Processed

Charcoal-Processed

Changes in Chemical Constituents

Changes in Kidney-Yang Tonifying Activities

Herba Cistanches—Vietnamese Name: Nhục Thung Dung

Processing

Changes in Chemical Constituents

Changes in Kidney-Yang Tonifying Activities

Semen Cuscutae—Vietnamese Name: Thỏ ty tử

Processing

Changes in Chemical Constituents

Changes in Kidney-Yang Tonifying Activities

Radix Dipsaci—Vietnamese Name: Tục Đoạn

Processing

Salt-Processed

White Wine-Processed

Changes in Chemical Constituents

Changes in Kidney-Yang Tonifying Activities

Discussion

Conclusion

Footnotes

Declaration of Conflicting Interests

Funding

ORCID iDs

References