TYPE Editorial

PUBLISHED 28 November 2022

DOI 10.3389/fphar.2022.1086049

Editorial: Applications of herbal

OPEN ACCESS medicine to control chronic
EDITED AND REVIEWED BY
Giuseppe Remuzzi,
Istituto di Ricerche Farmacologiche
kidney disease: Volume II
Mario Negri IRCCS, Italy

*CORRESPONDENCE Jianping Chen 1*, Karl W. K. Tsim 2 and Ying-Yong Zhao 3

Jianping Chen, 1
[email protected] Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese
Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine,
SPECIALTY SECTION Shenzhen, China, 2Division of Life Science and Center for Chinese Medicine, The Hong Kong University
This article was submitted to Renal of Science and Technology, Hong Kong SAR, China, 3Faculty of Life Science and Medicine, Northwest
Pharmacology, University, Xi’an, Shaanxi, China
a section of the journal
Frontiers in Pharmacology
KEYWORDS
RECEIVED 01 November 2022
ACCEPTED 17 November 2022 chronic kidney disease, herbal medicine, mechanism, active component, safety usage
PUBLISHED 28 November 2022

CITATION
Chen J, Tsim KWK and Zhao Y-Y (2022),
Editorial: Applications of herbal
medicine to control chronic kidney
Editorial on the Research Topic
disease: Volume II.
Front. Pharmacol. 13:1086049. Applications of herbal medicine to control chronic kidney disease:
doi: 10.3389/fphar.2022.1086049 Volume II
COPYRIGHT
© 2022 Chen, Tsim and Zhao. This is an
open-access article distributed under
the terms of the Creative Commons
Attribution License (CC BY). The use,
distribution or reproduction in other
forums is permitted, provided the Introduction
original author(s) and the copyright
owner(s) are credited and that the
original publication in this journal is Chronic kidney disease (CKD) is a leading cause of life lost worldwide, representing a
cited, in accordance with accepted global public health burden (Chen et al., 2019). The pathophysiological mechanisms
academic practice. No use, distribution
leading to progression of CKD include parenchymal cell loss, chronic inflammation,
or reproduction is permitted which does
not comply with these terms. fibrosis and reduced regenerative capacity of kidney (Ruiz-Ortega et al., 2020; Speer et al.,
2022). The complications of CKD, e.g., anemia and cardiovascular disease, are associated
with increased risks of death (Fishbane and Spinowitz, 2018; Ravid et al., 2021). The
prevalence and mortality of CKD are collectively increasing, illustrating the need for
efficacious therapeutic approaches. This situation therefore calls for novel therapies for
CKD and its complications to prevent disease progression and to prevent death. In recent
years, herbal medicine has represented additional therapeutic alternatives in the
management and treatment of numerous diseases, and which is attracting greater
attention and being applied to stop or reverse CKD progression. In this Research
Topic, our goal is to provide a forum to advance research of herbal medicine towards
CKD therapies. Twenty-nine contributions covering the listed Research Topics have been
collected to this Research Topic.

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Chen et al. 10.3389/fphar.2022.1086049

Reviews of herbal medicine in the articles are providing valuable references in supporting efficacy
treatment of kidney disease and mechanism of herbal medicine in kidney diseases.

Wang et al. summarized the theories and treatment strategies

of traditional Chinese medicine (TCM) in treating CKD. The Herbal medicine and its active ingredients
strategies and mechanisms of TCM against CKD from different for kidney disease
forms of medication, such as usage of single herb (Astragali
Radix, roots of Astragalus membranaceus), or herbal pairs Eleven articles are focused on the usage of single herb and the
(Astragali Radix-Angelicae Sinensis Radix Pair), or herbal identification of active ingredients within the herb in treating
formula (Zhenwu Tang). TCMs have major role in inhibiting kidney disease. Li et al. have elucidated the effects and
activation of myofibroblasts, infiltration of inflammatory cells, mechanisms of paeoniflorin, one of major bio-actives
trans-differentiation of epithelial cells to mesenchymal cells, and extracted from roots of Paeonia lactiflora on CKD skeletal
excessive deposition of extracellular matrix to improve renal muscle atrophy. The results have shown that paeoniflorin can
fibrosis through various mechanisms. Renal fibrosis, especially improve renal functions, calcium/phosphorus disorders and
tubulointerstitial fibrosis, is the final manifestation of CKD. Yu nutrition indexes in the nephrectomized CKD rats, and the
et al. have summarized the role of TGF-β/Smad signaling mechanism of which are involved in suppressing oxidative
pathway in tubulointerstitial fibrosis. Moreover, the authors stress and mitochondrial dysfunction, partially through the
have pointed out that natural products, including A. AMPK/SIRT1/PGC-1α pathway. Astragaloside IV, an active
membranaceus, Salvia miltiorrhiza, Poria cocos and Rheum ingredient of A. membranaceus was also found to have
palmatum, as well as their phytochemicals, i.e., astragaloside beneficial role in nephrectomized CKD model (He et al.). The
IV, salvianolic acid, poricoic acids, are exerting anti- results demonstrated that astragaloside IV attenuated intestinal
tubulointerstitial fibrosis effects by targeting TGF-β/Smad barrier dysfunction via AKT-GSK3β-β-catenin pathway in
signaling. Growing evidence has indicated that hyperuricemia peritoneal dialysis. Moreover, formononetin, another major
is an independent risk factor in development and progression of constituent from A. membranaceus, has been reported to
CKD, and therefore a review by Yang et al. has provided an improve albuminuria, renal tubular injury, and mitochondrial
overview of efficacy and mechanisms of TCM or natural products damage in streptozotocin-induced diabetic rats, and the
in hyperuricemia-induced CKD. The authors presented 11 herbs, mechanism of which was partly through regulating Sirt1/
such as Smilax china, Liriodendron chinense, Dendrobium PGC-1α pathway (Huang et al.). Supporting this notion, a
officinale and Rhododendron oldhamii, have renal-protective study by Zhang et al. further demonstrated the protective
effects on hyperuricemic nephropathy via lowering serum effect of calycosin, an active flavonoid of A. membranaceus,
excessive uric acid level. The mechanisms of which are on renal ischemia/reperfusion (I/R) injury. Calycosin was
involved in inhibiting activity of liver xanthine oxidoreductase found to improve kidney function and to reduce renal
and/or regulating expressions of renal urate transporters. inflammation responses, and the NF-κB-mediated
Podocyte injury is one of common causes of proteinuric inflammatory response via PPARγ/EGR1 pathway was
kidney diseases. Here, Lin et al. have discussed the potential involved. Ding et al. (2022) have found that total extract of
mechanism of TCM and its active components in protecting flowers of Abelmoschus manihot was able to attenuate the uric
podocytes, such as repairing podocyte injury, inhibiting podocyte acid-induced NRK-52E cell injury, mimicking a hyperuricemia
proliferation, reducing podocyte apoptosis and excretion, condition. The results showed that A. manihot protected against
maintaining podocyte skeleton structure and upregulating uric acid-induced cell injury through anti-pyroptotic effect by
podocyte-related protein expression, supporting the downregulating caspase-8/caspase-3/NLPR3 (NOD-like receptor
development of new therapeutics against primary podocytosis. thermal protein domain associated protein 3)/GSDME
In support of this notion, a review by Miao et al. has summed up (gasdermin E) signaling. Another study by Zhang et al. has
the applications of TCM such as Tripterygium wilfordii and A. revealed the therapeutic effect of urolithin A, a major
membranaceus for the treatment of membranous nephropathy, a intestinal metabolite of ellagitannins from a family of
renal-limited non-inflammatory autoimmune disease in the polyphenols presenting in fruits and nuts, in a fructose-
glomerulus. Wang et al. have summarized the role of induced hyperuricemic nephropathy mouse model, and the
metabolic reprogramming in diabetic kidney disease, one of effect of which was involved in impairing STING-NLRP3
the most common microvascular complications of diabetes axis-mediated inflammatory response via Parkin-dependent
mellitus. Furthermore, a meta-analysis of randomized mitophagy.
controlled trials was conducted by Fu et al. to clarify the Acute kidney injury (AKI) is one of significant risk factors in
effect of hydroxyl safflower yellow A (from Carthamus development of CKD, and three articles are exploring therapy for
tinctorius) on oxidative stress and inflammatory response in preventing AKI or delaying its progression to CKD. First, Dou
patients with diabetic kidney disease. Collectively, these review et al. have explored the protective role of S. miltiorrhiza and its

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Chen et al. 10.3389/fphar.2022.1086049

bioactive compound tanshinone IIA (TanIIA) in AKI. The Yishen Huashi (YSHS) granule, a herbal prescription mainly
authors reported that nuclear receptor family could be the composing of roots and rhizomes of Panax ginseng, roots of A.
target of S. miltiorrhiza in AKI treatment by a prediction membranaceus, rhizomes of Atractylodes macrocephala and P.
from network pharmacology. Furthermore, TanIIA was found cocos, ameliorated renal fibrosis and preserved the integrity of the
to improve cell necrosis proliferation and to reduce renal kidney filtration barrier, and the PI3K/AKT/mTOR pathway
inflammation by stimulating the expression of pregnane X participated in YSHS-modulated diabetic nephropathy rats.
receptor and inhibiting NF-κB signaling. Another study by Besides, Xu et al. have conducted a bibliometric and
Liu et al. investigated the effect of tilianin (acacetin-7- knowledge-map analysis to analyze the research status and
glucoside), a bio-active flavonoid glycoside isolated from application of herbal medicine for the treatment of CKD. The
various medicinal plants, e.g., Agastache rugosa, in results indicate that herbal medicine has a wide range of
I/R-induced AKI mice. The authors found that tilianin could pharmacological activities and therapeutic value for CKD.
reduce apoptosis after I/R-induced AKI by ERK/EGR1/ One article by Ni et al. has explored the nephrotoxicity of
BCL2L1 pathway. To further support the role of natural bavachin, one of the main toxic components in fruits of Psoralea
products in AKI, Yao et al. have evaluated the therapeutic corylifolia, and its prevention. The results confirmed that bavachin at
effect of oroxylin A, an active component of Scutellaria 0.5 μM could cause obvious renal fibrosis in vivo and in vitro, and
baicalensis, in I/R and cisplatin indued-AKI mice. The results which was associated with the activation of the TGFβ1/Smad3 and
showed that oroxylin A ameliorated tubular damage and Notch1/NICD signaling pathway. Furthermore, the authors
dramatically decreased serum creatinine and urea nitrogen, discovered that ginsenoside Rb1 exerted an outstanding effect
and the expressions of renal injury markers (Kim-1, Ngal) in against bavachin-induced renal fibrosis via suppressing ROS-
AKI mice, as well as attenuating AKI-to-CKD transition, and triggered endoplasmic reticulum stress. Another study by Wu
which was involved in maintaining PPARα-BNIP3 signaling- et al. evaluated the efficacy and hepatotoxicity of tripterygium
mediated mitochondrial homeostasis. In addition to AKI, Li et al. glycosides tablets extract from a well-known herb T. wilfordii
have investigated the protective effects of Phyllanthus niruri on in vivo. The findings showed that tripterygium glycosides
calcium oxalate-induce renal injury in mice, a urolithiasis or exhibited clear therapeutic efficacy in nephrotic syndrome rats,
kidney stones model. Ellagic acid was identified as the active but aggravated hepatotoxicity. The potential mechanism was
ingredient from P. niruri in inhibiting the increased expressions related to the significant increase of in vivo exposure of the six
of squalene monooxygenase (SQLE), stearoyl-CoA desaturase key components in nephrotic syndrome rats. Triptolide, wilforlide
(SCD) and 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 A, wilforgine, wilfortrine, wilfordine and wilforine were identified as
(GMGCS1) in oxalate-induced renal injury in HK-2 cells and active ingredients within tripterygium glycosides, whereas triptolide,
mice model. The article by Chen et al. has shown that saponins wilforgine, wilfortrine, and wilfordine were recognized as
from Panax notoginseng effectively alleviated steroid resistance in hepatotoxic components. Taken together, these studies will be
methylprednisolone induced steroid-resistant lupus nephritis useful for the clinical application of such herb.
mouse model through the regulation of lymphocyte-derived Apart from herbal medicine for kidney disease, four articles
exosomes. focusing on different aspects have been included in this Research
Four articles have focused on herbal medicine in a Topic. Du et al. have conducted a meta-analysis to evaluate the
formulated mixture for the treatment of kidney disease. Wang effectiveness of calcium dobesilate, a microcirculation-improving
et al. have evaluated the protective effects of Rehmannia glutinosa medication in diabetic kidney disease patients. The results
and Cornus officinalis, a herbal pairing from the famous Chinese showed that calcium dobesilate was effective and safe in
medicine prescription “Liuwei Dihuang Pill”, on adenine- patients with diabetic kidney disease, and the mechanism of
induced CKD rats. The results revealed that the combination which was involved in suppressing MAPK and chemokine
of these two herbs could modulate the composition of gut signaling pathways. Feng et al. have shown that the activation
microbiota and enhance barrier function to intervene CKD. of transient receptor potential ion channel 6 (TRPC6) by
Another herb-pair containing T. wilfordii and Trichosanthes angiotensin II, a strong vasoconstrictor active factor induced
kirilowii was found to have effect on diabetic kidney disease podocyte injury and participated in proteinuria of nephrotic
by improving insulin resistance, inflammation, and oxidative syndrome rat model induced by adriamycin, whereas losartan,
stress (Lu et al.). A study by Liu et al. investigated the an angiotensin receptor blocker and TRPC6-specific inhibitor
renoprotective effect of Jian-Pi-Yi-Shen (JPYS), a Chinese SAR7334 could effectively attenuate podocyte injury and
herbal decoction containing eight medicinal herbs, in adenine- proteinuria. Liu et al. have explored the therapeutic effect of
induced CKD rat model. The results showed that JPYS alleviated Jiawei Runjing decoction in the treatment of cryptozoospermia
renal dysfunction and fibrosis in CKD rats, and the mechanism through two-center prospective cohort study. The findings
of which might be related to the regulation of tryptophan indicated that Jiawei Runjing decoction could promote
metabolism and inhibition of aryl hydrocarbon receptor spermatogenesis in cryptozoospermia patients with varicocele,
signaling activation. Finally, Zhao et al. have shown that which might be closely related to improving the testicular

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Chen et al. 10.3389/fphar.2022.1086049

microenvironment. Besides, Yang et al. have characterized the Funding

differences between the cold and hot properties of Chinese herbs.
The results showed that the K value, a sensitive parameter could This work is supported by the Sanming Project of Medicine
reflect the cold and hot properties of Chinese herbs. in Shenzhen (SZZYSM202111002), Shenzhen Science and
Technology Program (JSGG20191129102216637,
JSGG20210802093208023 and ZDSYS201606081515458), and
Conclusion Traditional Chinese Medicine Bureau of Guangdong Province
(20231286).
This Research Topic collects 29 articles covering a wide range
of studies in the field of herbal medicine in controlling kidney
disease. These findings greatly improve our understanding on the Conflict of interest
therapeutic effects and mechanisms of herbal medicine in
preventing or reducing kidney damage and its related diseases. The authors declare that the research was conducted in the
These studies also highlight unique advantages in discovering absence of any commercial or financial relationships that could
potential candidate drugs from active ingredients within herbal be construed as a potential conflict of interest.
medicine. Thus, this topic can provide scientific evidence to
support the development of herbal medicine as therapeutic
strategies for the treatment of CKD. Publisher’s note
All claims expressed in this article are solely those of the
Author contributions authors and do not necessarily represent those of their affiliated
organizations, or those of the publisher, the editors and the
JC, KT, and YZ: Concept, design, literature search and reviewers. Any product that may be evaluated in this article, or
manuscript review. JC: acquisition of data, drafting the claim that may be made by its manufacturer, is not guaranteed or
manuscript. All authors have read and approved the manuscript. endorsed by the publisher.

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