1 Introduction

PRehmannia glutinosa, a crucial herb in Traditional Chinese Medicine (TCM), is highly esteemed for its diverse therapeutic properties. Integrating TCM with contemporary medical practices opens new avenues for fully utilizing the potential of traditional herbs like Rehmannia glutinosa. This study aims to explore modern therapies involving Rehmannia glutinosa, highlighting its integration into contemporary medicine.

Rehmannia glutinosa, belonging to the family Scrophulariaceae, is widely used in TCM to nourish Yin and invigorate the kidneys. It contains over 70 compounds, including iridoids, saccharides, and amino acids, which exhibit significant pharmacological actions on the blood, immune, endocrine, cardiovascular, and nervous systems (Zhang et al., 2008). Modern studies have identified its potential in managing conditions such as diabetes, hypertension, and neurodegenerative diseases, further solidifying its role in contemporary therapeutic practices (Hsu et al., 2014).

This study provides a comprehensive overview of the therapeutic applications of Rehmannia glutinosa in both TCM and modern medicine. As a traditional herb, Rehmannia glutinosa boasts a rich history and wide application; its specific usage and efficacy in various medical systems need systematic review and summary. Furthermore, an in-depth analysis of the pharmacological mechanisms of Rehmannia glutinosa is conducted to reveal the scientific basis of its effectiveness. By studying the chemical composition and pharmacological actions of Rehmannia glutinosa, we can better understand its mechanisms in different therapeutic fields, thereby providing theoretical support for its application in modern medicine. Additionally, the integration of Rehmannia glutinosa into contemporary medical treatments and its potential for new drug development are evaluated. With the rise of integrated traditional and Western medicine treatments, the application prospects of Rehmannia glutinosa in modern medicine are broad. This study will explore its application cases in modern clinical practice, analyze its potential drug development value, and propose future research directions.

2 Botanical Characteristics and Traditional Uses

2.1 Botanical description

Rehmannia glutinosa, commonly known as Chinese foxglove, is a perennial herb that belongs to the family Scrophulariaceae. It is characterized by its tuberous roots, which are the primary part used in traditional medicine. The plant has broad leaves and purple flowers, and it is typically found in China, Korea, and Japan (Zhang et al., 2008). The root, known as Radix Rehmanniae, can be used fresh or dried, and it is known for its sticky texture and sweet taste.

2.2 Historical and traditional uses in chinese medicine

Historically, Rehmannia glutinosa has been a staple in Traditional Chinese Medicine (TCM) for centuries. It is used to nourish Yin, replenish the blood, and invigorate the kidneys. Traditional texts describe its use in treating a variety of conditions such as anemia, dizziness, and menstrual disorders. The herb is often included in formulas for enhancing vitality and longevity (Tang and Eisenbrand, 1992).

In traditional Chinese medicine, Rehmannia glutinosa is often used in combination with other herbs to enhance its therapeutic effects. For example, it is a key ingredient in the famous formula Liu Wei Di Huang Wan, which is used to treat symptoms of kidney Yin deficiency such as tinnitus, night sweats, and dry mouth (Hsu et al., 2014).

2.3 Preparation and forms used in traditional medicine

Rehmannia glutinosa is prepared in various forms in TCM. The fresh root, known as Xian Di Huang, is often used to clear heat and cool the blood. The dried root, called Sheng Di Huang, is typically used for its nourishing and cooling properties. The processed root, known as Shu Di Huang, is steamed with rice wine, which enhances its tonic properties and makes it more suitable for nourishing the blood and kidneys (Yu et al., 2006).

Processing Rehmannia glutinosa involves nine cycles of steaming and drying, which significantly alters its chemical composition. This process increases the concentration of certain beneficial compounds, making the herb more effective for long-term tonic use (Chang et al., 2011).Rehmannia glutinosa is a versatile herb with a rich history in TCM, used in various forms to treat a wide range of ailments. Its preparation methods are critical to its effectiveness, making it a cornerstone of traditional herbal medicine.

3 Phytochemistry of Rehmannia glutinosa

3.1 Key bioactive compounds

Rehmannia glutinosa, a widely utilized herb in Traditional Chinese Medicine (TCM), contains a variety of bioactive compounds that contribute to its therapeutic effects. Key compounds identified in Rehmannia glutinosa include iridoids, phenylethanoid glycosides, saccharides, and amino acids. Notable iridoids such as catalpol and aucubin have been extensively studied for their pharmacological properties. Phenylethanoid glycosides like acteoside and echinacoside are known for their antioxidant, anti-inflammatory, and neuroprotective effects (Zhang et al., 2008). Other important compounds include rehmaionoside A, rehmannioside D, and various triterpenoids and flavonoids which have been linked to the herb's medicinal properties (Nguyen et al., 2020).

3.2 Extraction and identification techniques

The extraction and identification of bioactive compounds from Rehmannia glutinosa involve sophisticated techniques to ensure the purity and efficacy of the extracts. Common methods include solvent extraction, chromatography (such as HPLC and GC-MS), and spectrometry (including NMR and MS). These techniques allow for the isolation and structural elucidation of individual compounds. For example, high-pressure liquid chromatography (HPLC) coupled with quadrupole/time-of-flight mass spectrometry (QTOF-MS) has been used to profile metabolites and identify key phytotoxic metabolites in the herb (Zhang et al., 2019). Additionally, nuclear magnetic resonance (NMR) spectroscopy has been employed to determine the structures of isolated compounds from the aerial parts of the plant (Nguyen et al., 2020).

3.3 Comparative analysis of raw and processed Rehmannia

The processing of Rehmannia glutinosa significantly alters its chemical composition and enhances its therapeutic properties. Traditional processing methods involve steaming and drying the roots, which can convert certain compounds into more bioactive forms. For instance, catalpol and other iridoids undergo hydrolysis during processing, increasing the levels of monosaccharides such as glucose and galactose, which contribute to the enhanced medicinal quality of the processed herb (Chang et al., 2006). Additionally, processed Rehmannia glutinosa exhibits higher antioxidant activity compared to its raw counterpart, as demonstrated by increased levels of phenolic compounds and enhanced enzymatic activities (Manivannan et al., 2015). The differences in phytochemical profiles between raw and processed Rehmannia glutinosa underscore the importance of traditional processing techniques in maximizing the herb's therapeutic potential.

The phytochemistry of Rehmannia glutinosa encompasses a wide range of bioactive compounds that contribute to its medicinal value (Figure 1). Advanced extraction and identification techniques play a crucial role in isolating and characterizing these compounds. Furthermore, traditional processing methods significantly enhance the herb's efficacy, making Rehmannia glutinosa a vital component of both traditional and contemporary medicine.

4 Pharmacological Properties

Rehmannia glutinosa, a key herb in Traditional Chinese Medicine, exhibits a wide array of pharmacological properties that support its integration into modern therapeutic practices. This section explores the herb’s anti- inflammatory, antioxidant, immunomodulatory, and neuroprotective effects, as well as other pharmacological benefits.

4.1 Anti-inflammatory effects

Rehmannia glutinosa has significant anti-inflammatory properties. Studies have shown that the extract from Rehmannia glutinosa inhibits the secretion of inflammatory mediators such as nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-1 (IL-1) from activated macrophages and astrocytes (Sung et al., 2011; Liu et al., 2012). The bioactive component rehmapicrogenin has been identified as a key player in inhibiting NO production and reducing the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), further contributing to its anti-inflammatory effects (Liu et al., 2012).

4.2 Antioxidant activity

The antioxidant properties of Rehmannia glutinosa are well-documented. The steamed roots of the herb have been shown to enhance the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) in mouse auditory cells (Yu et al., 2006). These enzymes play a critical role in scavenging free radicals and reducing oxidative stress, which is beneficial in preventing cellular damage and aging.

4.3 Immunomodulatory functions

Rehmannia glutinosa exhibits strong immunomodulatory effects. Polysaccharides derived from the herb have been found to enhance the proliferation and activation of lymphocytes and dendritic cells, boosting the immune response. In vitro and in vivo studies have demonstrated that these polysaccharides increase the production of cytokines and enhance the activity of natural killer (NK) cells, thereby improving the body's defense against infections and cancer (Xu et al., 2017; Feng et al., 2020).

4.4 Neuroprotective effects

Rehmannia glutinosa also has notable neuroprotective properties. The iridoid glycoside catalpol, extracted from the herb, has been shown to protect neurons by inhibiting apoptosis and oxidative stress. Catalpol enhances mitochondrial biogenesis and activates the PI3K/Akt pathway, which is crucial for neuronal survival and function (Huang et al., 2022). Additionally, catalpol has been reported to improve cognitive function and memory, suggesting its potential in treating neurodegenerative diseases such as Alzheimer’s (Bhattamisra et al., 2019).

4.5 Other pharmacological benefits

Beyond its anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective effects, Rehmannia glutinosa offers additional health benefits. The herb has been found to ameliorate hyperglycemia and hyperlipemia, reduce vascular inflammation, and improve insulin sensitivity in diabetic models (Zhou et al., 2015). Moreover, its polysaccharides have shown potential as mucosal adjuvants, enhancing immune responses in the lungs and providing protective effects against respiratory infections and tumors (Kwak et al., 2018). Rehmannia glutinosa demonstrates a broad spectrum of pharmacological properties that make it a valuable component in both traditional and modern medical treatments. Its integration into contemporary therapeutic practices could lead to more effective and comprehensive health management strategies.

5 Integration with Contemporary Medicine

5.1 Synergistic effects with modern pharmaceuticals

Rehmannia glutinosa has demonstrated significant potential in enhancing the efficacy of modern pharmaceuticals. Studies show that its extracts can synergize with conventional drugs to improve therapeutic outcomes. For instance, the polysaccharide fraction of R. glutinosa has been shown to potentiate the effects of antidiabetic drugs by enhancing insulin secretion and reducing blood glucose levels (Zhou et al., 2015). Additionally, its combination with chemotherapeutic agents has demonstrated reduced side effects and enhanced anticancer efficacy through mechanisms such as the inhibition of lipid peroxidation and scavenging of free radicals (Yu et al., 2006).

5.2 Clinical trials and evidence-based studies

Several clinical trials and evidence-based studies have evaluated the efficacy of R. glutinosa in treating various conditions. One significant study found that R. glutinosa extracts significantly reduced waist circumference in obese women, possibly through the modulation of gut microbiota (Han et al., 2015). Another study highlighted its neuroprotective effects in a rat model of cognitive impairment, where it was shown to improve memory and reduce inflammation (Lee et al., 2011).

5.3 Application in treating modern diseases

R. glutinosa has been extensively studied for its hypoglycemic effects. It has been shown to improve blood glucose levels, enhance insulin secretion, and reduce oxidative stress in diabetic models (Zhou et al., 2015). Its polysaccharides are particularly effective in ameliorating hyperglycemia and related complications.

The herb is traditionally used to treat kidney ailments. Modern research has confirmed its efficacy in reducing the progression of renal failure. R. glutinosa extracts have been found to decrease serum creatinine levels, proteinuria, and glomerulosclerosis in animal models of kidney disease (Lee et al., 2009).

The neuroprotective properties of R. glutinosa make it a promising candidate for treating neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. Studies have shown that it can improve cognitive function and protect against neuronal damage by modulating inflammatory responses and enhancing antioxidant enzyme activities (Lee et al., 2011).

5.4 Case studies and clinical reports

Several case studies and clinical reports provide practical insights into the application of R. glutinosa in modern medicine. For example, in a study on the effects of R. glutinosa on bone health, it was found to prevent bone loss and improve bone density in ovariectomized rats, suggesting its potential use in treating osteoporosis (Figure 2) (Lim and Kim, 2013; Gong et al., 2019). Another report detailed the use of R. glutinosa in treating renal failure, highlighting its ability to improve kidney function and reduce symptoms of nephropathy (Lee et al., 2009). These examples illustrate the broad therapeutic potential of Rehmannia glutinosa when integrated with contemporary medical practices, paving the way for its wider acceptance and use in modern healthcare.

6 Safety and Toxicology

6.1 Toxicological studies and findings

Recent studies have shown that while Rehmannia glutinosa (RG) is widely used in traditional and modern medicine, there are potential toxicological risks associated with its use. For instance, certain toxic components in RG may pose safety concerns, as these toxic substances are produced through the plant's metabolic processes and may threaten human health (Yang et al., 2020). Additionally, some studies have indicated that specific components of RG may induce cytotoxic reactions under certain conditions, warranting caution in its clinical use (Huang et al., 2022).

6.2 Dosage and administration guidelines

The dosage and administration of RG vary between traditional Chinese medicine (TCM) and modern medical practices. In TCM, RG is typically prepared in various forms such as raw Rehmannia, cooked Rehmannia, and Rehmannia decoctions, with each form having specific dosages and usage frequencies. In modern medicine, RG extracts are widely used in various studies and treatments. For example, one study demonstrated that RG extract effectively protects inner ear cells from cisplatin-induced cytotoxicity at a recommended dosage range of 5-50 µg/ml (Kwon et al., 2019). However, specific dosages and usage methods should be adjusted according to the patient's condition and the type of disease to ensure safety and efficacy.

6.3 Potential side effects and contraindications

Despite the therapeutic benefits of RG, there are potential side effects and contraindications associated with its use. For instance, studies have shown that RG may cause gastrointestinal discomfort, such as diarrhea and abdominal pain. Additionally, RG may interact with certain medications, affecting their metabolism and efficacy. For example, RG may induce the cytochrome P450 enzyme system, altering the metabolism and toxicity of some drugs (Liu et al., 2020). Therefore, it is essential to consider the potential side effects and contraindications when using RG for treatment, especially for patients with chronic diseases or those taking other medications. While RG shows significant therapeutic effects in treating various diseases, its use should be approached with caution, particularly concerning dosage, administration methods, and potential side effects and contraindications. The research findings discussed in this section provide valuable references for the safe application of RG in modern medicine.

7 Future Directions and Research Opportunities

7.1 Emerging trends in Rehmannia glutinosa research

Recent studies on Rehmannia glutinosa have unveiled numerous pharmacological potentials, particularly in managing chronic diseases like diabetes, hypertension, and neurodegenerative disorders. The herb's polysaccharides have demonstrated significant immunomodulatory effects, enhancing lymphocyte proliferation and dendritic cell function (Huang et al., 2013). Furthermore, the genetic diversity of Rehmannia glutinosa has been explored through microsatellite loci characterization, providing valuable insights for breeding programs aimed at improving therapeutic efficacy (Jiao et al., 2015). These advancements indicate a promising future for integrating Rehmannia glutinosa into modern medical practices.

7.2 Technological advances in extraction and analysis

The development of new extraction and analytical technologies has significantly enhanced the understanding of Rehmannia glutinosa's bioactive compounds. Techniques such as Fourier transform near-infrared (FT-NIR) analysis have been used to compare chemical constituents in different cultivation methods, aiding in the identification of optimal growth conditions (Kim et al., 2020). Additionally, high-throughput sequencing and bioinformatics analyses have provided insights into the molecular mechanisms underlying tuberous root development, essential for genetic engineering and breeding programs (Sun et al., 2015). These technological advances pave the way for more precise and efficient use of Rehmannia glutinosa in therapeutic applications.

7.3 Potential for new therapeutic applications

The diverse pharmacological activities of Rehmannia glutinosa suggest its potential for new therapeutic applications. For instance, its extracts have shown efficacy in reducing waist circumference and modulating gut microbiota in obese women, indicating its potential as an anti-obesity agent (Han et al., 2015). Moreover, Rehmannia glutinosa has demonstrated protective effects against atopic dermatitis and renal failure, showcasing its broad therapeutic scope (Sung et al., 2011; Lee et al., 2009). These findings highlight the need for further clinical trials to explore and validate these potential applications.

7.4 Gaps in current knowledge and future research needs

Despite the significant progress, there are still several gaps in the current knowledge of Rehmannia glutinosa. One major area that requires further exploration is the detailed mechanism of action of its bioactive compounds. Additionally, while some studies have identified potential autotoxic compounds and microbes associated with replant problems, more research is needed to fully understand these interactions and develop effective solutions (Zhang et al., 2016). Another critical area is the long-term safety and efficacy of Rehmannia glutinosa in various therapeutic applications, which requires comprehensive clinical trials. Future research should focus on these aspects to fully harness the therapeutic potential of Rehmannia glutinosa.

8 Concluding Remarks

Rehmannia glutinosa, a traditional Chinese herb, has shown significant therapeutic potential across various medical conditions. Studies have demonstrated its renoprotective effects, where it significantly reduced serum creatinine levels, proteinuria, and glomerulosclerosis in progressive renal failure. This effect is likely mediated by suppressing angiotensin II and regulating TGF-beta1 and type IV collagen expression. Additionally, Rehmannia glutinosa has shown neuroprotective benefits, improving memory impairments and cognitive functions in models of neurodegenerative diseases by enhancing cholinergic activity and reducing inflammation.

The herb also exhibits substantial anti-inflammatory and immune-modulating properties. In atopic dermatitis models, Rehmannia glutinosa extract has been effective in reducing dermatitis scores, ear thickness, and serum histamine levels, showcasing its anti-inflammatory capabilities. Furthermore, it enhances immune responses by activating natural killer cells and dendritic cells, contributing to its broad immunomodulatory effects.

Moreover, Rehmannia glutinosa has shown potential in promoting bone health. It prevents bone loss and enhances bone formation in models of osteoporosis and diabetes-induced bone deterioration through the regulation of the IGF-1/PI3K/mTOR pathways. Metabolic benefits of Rehmannia glutinosa include its role in reducing waist circumference in obese individuals, potentially by modulating gut microbiota, and its efficacy in managing blood glucose levels in diabetic models.

The integration of traditional Chinese medicine (TCM) and modern medical practices offers a comprehensive approach to healthcare, leveraging the strengths of both systems. Combining Rehmannia glutinosa with conventional treatments could enhance therapeutic outcomes, especially in chronic conditions such as renal failure, neurodegenerative diseases, and metabolic disorders. TCM's holistic approach can complement modern medicine by addressing the root causes of diseases and promoting overall well-being. Utilizing herbal therapies like Rehmannia glutinosa may reduce the reliance on synthetic drugs, potentially lowering the incidence of adverse effects and improving patient compliance. Continued research into the pharmacological mechanisms and active compounds of Rehmannia glutinosa can lead to the development of novel therapies that bridge traditional and modern practices.

Integrating Rehmannia glutinosa into modern therapeutic regimens presents a promising avenue for enhancing patient care. Future research should focus on conducting rigorous clinical trials to validate the efficacy and safety of Rehmannia glutinosa in various medical conditions. Mechanistic studies exploring the molecular mechanisms underlying its therapeutic effects are crucial for identifying potential targets for drug development. Developing standardized extracts and formulations will ensure consistent quality and potency in clinical applications. Additionally, increasing awareness among healthcare providers and patients about the benefits of integrating TCM with modern medicine can foster acceptance and utilization. By embracing the strengths of both traditional and contemporary medicine, we can provide more effective, holistic, and patient-centered healthcare solutions.

Acknowledgments

I extend my sincere thanks to two anonymous peer reviewers for their invaluable feedback on the initial draft of this manuscript.

Conflict of Interest Disclosure

The author affirms that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

References

Bhattamisra S., Yap K., Rao V., and Choudhury H., 2019, Multiple biological effects of an iridoid glucoside, catalpol, and its underlying molecular mechanisms, Biomolecules, 10(1): 32.

https://doi.org/10.3390/biom10010032

Chang W., Choi Y., Heijden R., Lee M., Lin M., Kong H., Kim H., Verpoorte R., Hankemeier T., Greef J., and Wang M., 2011, Traditional processing strongly affects metabolite composition by hydrolysis in Rehmannia glutinosa roots, Chemical & Pharmaceutical Bulletin, 59(5): 546-552.

https://doi.org/10.1248/CPB.59.546

Chang W., Thissen U., Ehlert K., Koek M., Jellema R., Hankemeier T., Greef J., and Wang M., 2006, Effects of growth conditions and processing on Rehmannia glutinosa using fingerprint strategy, Planta Medica, 72(5): 458-467.

https://doi.org/10.1055/S-2005-916241

Feng J., Cai Z., Zhang X., Chen Y., Chang X., Wang X., Qin C., Yan X., Ma X., Zhang J., and Nie G., 2020, The effects of oral Rehmannia glutinosa polysaccharide administration on immune responses, antioxidant activity and resistance against aeromonas hydrophila in the common carp, Cyprinus carpio L., Frontiers in Immunology, 11: 904.

https://doi.org/10.3389/fimmu.2020.00904

Gong W., Zhang N., Cheng G., Zhang Q., He Y., Shen Y., Zhang Q., Zhu B., Zhang Q., and Qin L., 2019, Rehmannia glutinosa libosch extracts prevent bone loss and architectural deterioration and enhance osteoblastic bone formation by regulating the IGF-1/PI3K/mTOR pathway in streptozotocin-induced diabetic rats, International Journal of Molecular Sciences, 20(16): 3964.

https://doi.org/10.3390/ijms20163964

Han K., Bose S., Kim Y., Chin Y., Kim B., Wang J., Lee J., and Kim H., 2015, Rehmannia glutinosa reduced waist circumferences of Korean obese women possibly through modulation of gut microbiota, Food & Function, 6(8): 2684-2692 .

https://doi.org/10.1039/c5fo00232j

Hsu P., Tsai Y., Lai J., Wu C., Lin S., and Huang C., 2014, Integrating traditional Chinese medicine healthcare into diabetes care by reducing the risk of developing kidney failure among type 2 diabetic patients: a population-based case control study, Journal of Ethnopharmacology, 156: 358-364.

https://doi.org/10.1016/j.jep.2014.08.029

Huang Y., Ando H., Tsujino M., Yoshihara K., Zhang L., and Sasaki Y., 2022, Study on catalpol content in rehmannia glutinosa root, an important ingredient in kampo prescriptions, Biological & Pharmaceutical Bulletin, 45(7): 955-961 .

https://doi.org/10.1248/bpb.b21-01095

Huang Y., Jiang C., Hu Y., Zhao X., Shi C., Yu Y., Liu C., Tao Y., Pan H., Feng Y., Liu J., Wu Y., and Wang D., 2013, Immunoenhancement effect of Rehmannia glutinosa polysaccharide on lymphocyte proliferation and dendritic cell, Carbohydrate Polymers, 96(2): 516-521 .

https://doi.org/10.1016/j.carbpol.2013.04.018

Huang Z., Gong J., Lin W., Feng Z., Ma Y., Tu Y., Cai X., Liu J., Lv C., Lv X., Wu Q., Lu W., Zhao J., Ying Y., Li S., Ni W., and Chen H., 2022, Catalpol as a component of Rehmannia glutinosa protects spinal cord injury by inhibiting endoplasmic reticulum stress-mediated neuronal apoptosis, Frontiers in Pharmacology, 13: 860757.

https://doi.org/10.3389/fphar.2022.860757

Jiao Z., Cheng Y., Wang H., Lei C., Wang G., and Han L., 2015, Isolation and characterization of microsatellite loci in Rehmannia glutinosa (Scrophulariaceae), a medicinal herb, Applications in Plant Sciences, 3(10): 1500054.

https://doi.org/10.3732/apps.1500054

Kim Y., Komakech R., Jeong D., Park Y., Lee T., Kim K., Lee A., Moon B., and Kang Y., 2020, Verification of the field productivity of Rehmannia glutinosa (Gaertn.) DC. developed through optimized in vitro culture method, Plants, 9(3): 317.

https://doi.org/10.3390/plants9030317

Kwak M., Yu K., Lee P., and Jin J., 2018, Rehmannia glutinosa polysaccharide functions as a mucosal adjuvant to induce dendritic cell activation in mediastinal lymph node, International Journal of Biological Macromolecules, 120: 1618-1623 .

https://doi.org/10.1016/j.ijbiomac.2018.09.187

Kwon Y., Yu S., Choi G., Kim J., Baik M., Su S., and Kim W., 2019, Puffing of Rehmannia glutinosa enhances anti-oxidant capacity and down-regulates IL-6 production in RAW 264.7 cells, Food Science and Biotechnology, 28: 1235-1240.

https://doi.org/10.1007/s10068-019-00566-z

Lee B., Shim I., Lee H., and Hahm D., 2011, Rehmannia glutinosa ameliorates scopolamine-induced learning and memory impairment in rats, Journal of Microbiology and Biotechnology, 21(8): 874-883 .

https://doi.org/10.4014/JMB.1104.04012

Lim D., and Kim Y., 2013, Dried root of Rehmannia glutinosa prevents bone loss in ovariectomized rats, Molecules, 18: 5804-5813.

https://doi.org/10.3390/molecules18055804

Liu C., Cheng L., Ko C., Wong C., Cheng W., Cheung D., Leung P., Fung K., and Lau C., 2012, Bioassay-guided isolation of anti-inflammatory components from the root of Rehmannia glutinosa and its underlying mechanism via inhibition of iNOS pathway, Journal of Ethnopharmacology, 143(3): 867-875 .

https://doi.org/10.1016/j.jep.2012.08.012

Liu W., Yin D., Zhang T., Qiao Q., Yang Y., and Wang W., 2020, Phytochemical profiles and antioxidant activity of Rehmannia glutinosa from different production locations, Chemistry & Biodiversity, 17(8): e2000341.

https://doi.org/10.1002/cbdv.202000341

Manivannan A., Soundararajan P., Halimah N., Ko C., and Jeong B., 2015, Blue LED light enhances growth, phytochemical contents, and antioxidant enzyme activities of Rehmannia glutinosa cultured in vitro, Horticulture, Environment, and Biotechnology, 56: 105-113.

https://doi.org/10.1007/s13580-015-0114-1

Nguyen H., Dan T., Uto T., Ohta T., Watanabe H., and Shoyama Y., 2020, Phytochemical profile of the aerial parts of Rehmannia glutinosa liboschitz var. purpurea Makino, Pharmacognosy Magazine, 16: 128-131.

https://doi.org/10.4103/pm.pm_243_19

Sun P., Xiao X., Duan L., Guo Y., Qi J., Liao D., Zhao C., Liu Y., Zhou L., and Li X., 2015, Dynamic transcriptional profiling provides insights into tuberous root development in Rehmannia glutinosa, Frontiers in Plant Science, 6: 396.

https://doi.org/10.3389/fpls.2015.00396

Sung Y., Yoon T., Jang J., Park S., and Kim H., 2011, Topical application of Rehmannia glutinosa extract inhibits mite allergen-induced atopic dermatitis in NC/Nga mice, Journal of Ethnopharmacology, 134(1): 37-44 .

https://doi.org/10.1016/j.jep.2010.11.050

Tang W., and Eisenbrand G., 1992, Rehmannia glutinosa Libosch, Chinese Drugs of Plant Origin, Springer, Berlin, Heidelberg, pp.849-854.

https://doi.org/10.1007/978-3-642-73739-8_106

Waisundara V., Huang M., Hsu A., Huang D., and Tan B., 2008, Characterization of the anti-diabetic and antioxidant effects of Rehmannia glutinosa in streptozotocin-induced diabetic Wistar rats, The American journal of Chinese medicine, 36(6): 1083-1104 .

https://doi.org/10.1142/S0192415X08006594

Xu L., Zhang W., Zeng L., and Jin J., 2017, Rehmannia glutinosa polysaccharide induced an anti-cancer effect by activating natural killer cells, International Journal of Biological Macromolecules, 105(1): 680-685 .

https://doi.org/10.1016/j.ijbiomac.2017.07.090

Yang Y., Zhang Z., Li R., Yi Y., Yang H., Wang C., Wang Z., and Liu Y., 2020, RgC3H involves in the biosynthesis of allelopathic phenolic acids and alters their release amount in Rehmannia glutinosa roots, Plants, 9(5): 567.

https://doi.org/10.3390/plants9050567

Yu H., Kim Y., Jung S., Shin M., Park R., So H., Kim K., Lee D., and You Y., 2006, Rehmannia glutinosa activates intracellular antioxidant enzyme systems in mouse auditory cells, The American Journal of Chinese Medicine, 34(6) 1083-1093.

https://doi.org/10.1142/S0192415X06004545

Yu H., Seo S., Kim Y., Lee H., Park R., So H., Jang S., and You Y., 2006, Protective effect of Rehmannia glutinosa on the cisplatin-induced damage of HEI-OC1 auditory cells through scavenging free radicals, Journal of Ethnopharmacology, 107(3) 383-388.

https://doi.org/10.1016/J.JEP.2006.03.024

Zhang B., Li X., Wang F., Li M., Zhang J., Gu L., Zhang L., Tu W., and Zhang Z., 2016, Assaying the potential autotoxins and microbial community associated with Rehmannia glutinosa replant problems based on its ‘autotoxic circle’, Plant and Soil, 407: 307-322.

https://doi.org/10.1007/s11104-016-2885-2

Zhang B., Weston P., Gu L., Zhang B., Li M., Wang F., Tu W., Wang J., Weston L., and Zhang Z., 2019, Identification of phytotoxic metabolites released from Rehmannia glutinosa suggest their importance in the formation of its replant problem, Plant and Soil, 441: 439-454.

https://doi.org/10.1007/s11104-019-04136-4

Zhang R., Li M., and Jia Z., 2008, Rehmannia glutinosa: review of botany, chemistry and pharmacology, Journal of Ethnopharmacology, 117(2): 199-214 .

https://doi.org/10.1016/j.jep.2008.02.018

Zhou J., Xu G., Yan J., Li K., Bai Z., Cheng W., and Huang K., 2015, Rehmannia glutinosa (Gaertn.) DC. polysaccharide ameliorates hyperglycemia, hyperlipemia and vascular inflammation in streptozotocin-induced diabetic mice, Journal of Ethnopharmacology, 164: 229-238.

https://doi.org/10.1016/j.jep.2015.02.026